Progesterone

Identification

Summary

Progesterone is a hormone used for a variety of functions, including contraception, control of abnormal uterine bleeding, maintenance of pregnancy, and prevention of endometrial hyperplasia.

Brand Names
Bijuva, Crinone, Endometrin, Prochieve, Prometrium
Generic Name
Progesterone
DrugBank Accession Number
DB00396
Background

Progesterone is a hormone that occurs naturally in females, and is essential for endometrial receptivity, embryo implantation, and the successful establishment of pregnancy. A low progesterone concentration or an insufficient response to progesterone can cause infertility and pregnancy loss 7. Progesterone is used in various contraceptive preparations to prevent ovulation and fertilization 15, 8 as well as in other formulations to promote and support pregnancy. Please see Medroxyprogesterone acetate, Megestrol acetate, Dydrogesterone and Hydroxyprogesterone entries for information on various other forms of progesterone.

Pharmaceutical progesterone is made from a plant source as a starting material and is chemically identical to progesterone of human ovarian origin Label. Progesterone is available in gelatinized capsule form, vaginal gel form, tablet form, vaginal insert form, and injection form, all used for various purposes Label,20,22,21,23.

Type
Small Molecule
Groups
Approved, Vet approved
Structure
Weight
Average: 314.4617
Monoisotopic: 314.224580204
Chemical Formula
C21H30O2
Synonyms
  • (S)-4-Pregnene-3,20-dione
  • (S)-Pregn-4-en-3,20-dione
  • (S)-Progesterone
  • 17alpha-Progesterone
  • 17α-progesterone
  • 4-Pregnene-3,20-dione
  • Agolutin
  • Akrolutin
  • Corpus Luteum Hormone
  • delta(4)-Pregnene-3,20-dione
  • Gelbkörperhormon
  • Luteohormone
  • Lutogynon
  • Pregn-4-ene-3,20-dione
  • Progesteron
  • Progesterona
  • Progestérone
  • Progesterone
  • Progesteronum
External IDs
  • BP 14
  • NSC-64377
  • NSC-9704
  • U 3672

Pharmacology

Indication

Gelatinized capsules

The gelatinized capsules are indicated for use in the prevention of endometrial hyperplasia in non-hysterectomized postmenopausal women who are receiving conjugated estrogens tablets. They are also indicated for use in secondary amenorrhea Label.

Vaginal gel

Progesterone gel (8%) is indicated as progesterone supplementation or replacement as part of an Assisted Reproductive Technology (“ART”) treatment for infertile women with progesterone deficiency. The lower concentration progesterone gel (4%) is used in the treatment of secondary amenorrhea, with the use of the 8% concentration if there is no therapeutic response to the 4% gel 20.

Vaginal insert

This form is indicated to support embryo implantation and early pregnancy by supplementation of corpus luteal function as part of an Assisted Reproductive Technology (ART) treatment program for infertile women 21.

Injection (intramuscular)

This drug is indicated in amenorrhea and abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, such as submucous fibroids or uterine cancer 23.

Tablets, contraceptive

The tablet form of progesterone in contraceptive formulations is indicated for the prevention of pregnancy 22.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofAbnormal uterine bleeding•••••••••••••••••••••
Treatment ofAmenorrhea•••••••••••••••• •••••••••
Prevention ofEndometrial hyperplasia caused by conjugated estrogen••••••••••••••••••••••••••
Used in combination to treatModerate to severe vasomotor symptomsCombination Product in combination with: Estradiol (DB00783)•••••••••••••••••••••••••••••
Prevention ofPregnancy••••••••••••
Associated Therapies
Contraindications & Blackbox Warnings
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Pharmacodynamics

Progesterone, depending on concentration and dosage form, and timing of exposure may have several pharmacodynamic effects. These actions, according, to various preparations, are listed below:

General effects

Progesterone is the main hormone of the corpus luteum and the placenta. It acts on the uterus by changing the proliferative phase to the secretory phase of the endometrium (inner mucous lining of the uterus). This hormone, stimulated by a hormone called luteinizing hormone (LH) is the main hormone during the secretory phase to prepare the corpus luteum and the endometrium for implantation of a fertilized ovum. As the luteal phase concludes, the progesterone hormone sends negative feedback to the anterior pituitary gland in the brain to decrease FSH (follicle stimulating hormone) and LH (luteinizing hormone) levels. This prevents ovulation and maturation of oocytes (immature egg cells). The endometrium then prepares for pregnancy by increasing its vascularity (blood vessels) and stimulating mucous secretion. This process occurs by progesterone stimulating the endometrium to decrease endometrial proliferation, leading to a decreased uterine lining thickness, developing more complex uterine glands, collecting energy in the form of glycogen, and providing more uterine blood vessel surface area suitable for supporting a growing embryo. As opposed to cervical mucous changes observed during the proliferative phase and ovulation, progesterone decreases and thickens the cervical mucus, rendering it less elastic. This change occurs because the fertilization time period has passed, and a specific consistency of mucous amenable to sperm entry is no longer required 16.

Gelatinized capsules

Progesterone capsules are an oral dosage form of micronized progesterone which, chemically identical to progesterone of ovarian origin. Progesterone capsules have all the properties of endogenous progesterone with induction of a secretory phase endometrium with gestagenic, antiestrogenic, slightly antiandrogenic and anti-aldosterone effects 24. Progesterone opposes the effects of estrogen on the uterus, and is beneficial in women with unopposed estrogen exposure, which carries an increased risk of malignancy 24.

Vaginal gel and vaginal insert

The gel preparation mimics the effects of naturally occurring progesterone. In the presence of adequate levels of estrogen, progesterone converts a proliferative endometrium into secretory endometrium. This means that the endometrium changes from a growing and thickening stage into a subsequent preparation stage for pregnancy, which involves further preparatory changes. Progesterone is necessary for the development of decidual tissue (specialized tissue amenable to supporting a possible pregnancy). Progesterone is required to increase endometrial receptivity for the implantation of a fertilized embryo. Once an embryo is implanted, progesterone helps to maintain the pregnancy 20.

Injection (intramuscular)

Intramuscularly injected progesterone increases serum progesterone and aids in the prevention of endometrial tissue overgrowth due to unopposed estrogen (which leads to abnormal uterine bleeding and sometimes uterine cancer) 18, 25. In the absence or deficiency of progesterone, the endometrium continually proliferates, eventually outgrowing its limited blood supply, shedding incompletely, and leading to abnormal and/or profuse bleeding as well as malignancy 18.

Tablets, contraceptive

Progesterone-only contraceptive tablets prevent conception by suppressing ovulation in about half of users, causing a thickening of cervical mucus to inhibit sperm movement, lowering the midcycle LH and FSH hormone peaks, slowing the movement of the ovum through the fallopian tubes, and causing secretory changes in the endometrium as described above 22.

Mechanism of action

Progesterone binds and activates its nuclear receptor, PR, which plays an important part in the signaling of stimuli that maintain the endometrium during its preparation for pregnancy.

Progesterone receptor (PR) is a member of the nuclear/steroid hormone receptor (SHR) family of ligand-dependent transcription factors that is expressed primarily in female reproductive tissue as well as the central nervous system. As a result of its binding its associated steroid hormone, progesterone, the progesterone receptor (PR) modulates the expression of genes that regulate the development, differentiation, and proliferation of target tissues 14. In humans, PR is found to be highly expressed in the stromal (connective tissue) cells during the secretory phase and during pregnancy 10.

Progesterone may prevent pregnancy by changing the consistency of cervical mucus to be unfavorable for sperm penetration, and by inhibiting follicle-stimulating hormone (FSH), which normally causes ovulation. With perfect use, the first-year failure rate for progestin-only oral contraceptives is approximately 0.5%. The typical failure rate, however, is estimated to be approximately 5%, due to late or missed pills 22.

TargetActionsOrganism
AProgesterone receptor
agonist
Humans
AMineralocorticoid receptor
antagonist
agonist
Humans
UEstrogen receptor
agonist
inhibitor
downregulator
Humans
USteroid 17-alpha-hydroxylase/17,20 lyase
substrate
inhibitor
Humans
UKappa-type opioid receptor
activator
potentiator
Humans
UAlpha-1-acid glycoprotein 1
binder
Humans
UGlucocorticoid receptor
partial agonist
Humans
UAndrogen receptor
agonist
potentiator
Humans
USex hormone-binding globulin
binder
potentiator
Humans
UEstrogen receptor beta
agonist
downregulator
Humans
Absorption

Oral micronized capsules

Following oral administration of progesterone in the micronized soft-gelatin capsule formulation, peak serum concentration was achieved in the first 3 hours. The absolute bioavailability of micronized progesterone is unknown at this time. In postmenopausal women, serum progesterone concentration increased in a dose-proportional and linear fashion after multiple doses of progesterone capsules, ranging from 100 mg/day to 300 mg/day Label.

IM administration

After intramuscular (IM) administration of 10 mg of progesterone in oil, the maximum plasma concentrations were achieved in about 8 hours post-injection and plasma concentrations stayed above baseline for approximately 24 hours post-injection. Injections of 10, 25, and 50 mg lead to geometric mean values for maximum plasma concentration (CMAX) of 7, 28, and 50 ng/mL, respectively 25. Progesterone administered by the intramuscular (IM) route avoids significant first-pass hepatic metabolism. As a result, endometrial tissue concentrations of progesterone achieved with IM administration are higher when compared with oral administration. Despite this, the highest concentrations of progesterone in endometrial tissue are reached with vaginal administration 11.

Note on oral contraceptive tablet absorption

Serum progestin levels peak about 2 hours after oral administration of progesterone-only contraceptive tablets, followed by rapid distribution and elimination. By 24 hours after drug administration, serum levels remain near the baseline, making efficacy dependent upon strict adherence to the dosing schedule. Large variations in serum progesterone levels occur among individuals. Progestin-only administration leads to lower steady-state serum progestin levels and a shorter elimination half-life than concurrent administration with estrogens 22.

Volume of distribution

When administered vaginally, progesterone is well absorbed by uterine endometrial tissue, and a small percentage is distributed into the systemic circulation. The amount of progesterone in the systemic circulation appears to be of minimal importance, especially when implantation, pregnancy, and live birth outcomes appear similar for intramuscular and vaginal administration of progesterone 11.

Protein binding

96%-99% bound to serum proteins, primarily to serum albumin (50%-54%) and transcortin (43%-48%) Label.

Metabolism

Progesterone is mainly metabolized by the liver. After oral administration, the major plasma metabolites found are 20 a hydroxy-Δ4 a-prenolone and 5 a-dihydroprogesterone. Some progesterone metabolites are found excreted in the bile and these metabolites may be deconjugated and subsequently metabolized in the gut by reduction, dehydroxylation, and epimerization Label. The major plasma and urinary metabolites are comparable to those found during the physiological progesterone secretion of the corpus luteum 24.

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Route of elimination

Progesterone metabolites are excreted mainly by the kidneys. Urinary elimination is observed for 95% of patients in the form of glycuroconjugated metabolites, primarily 3 a, 5 ß–pregnanediol (pregnandiol) 24. The glucuronide and sulfate conjugates of pregnanediol and pregnanolone are excreted in the urine and bile. Progesterone metabolites, excreted in the bile, may undergo enterohepatic recycling or may be found excreted in the feces.

Half-life

Absorption half-life is approximately 25-50 hours and an elimination half-life of 5-20 minutes (progesterone gel) 20.

Progesterone, administered orally, has a short serum half-life (approximately 5 minutes). It is rapidly metabolized to 17-hydroxyprogesterone during its first pass through the liver 11.

Clearance

Apparent clearance

1367 ± 348 (50mg of progesterone administered by vaginal insert once daily) 11.

106 ± 15 L/h (50mg/mL IM injection once daily) 11.

Adverse Effects
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Toxicity

Intraperitoneal LD50 (rat): 327 mg/kg MSDS.

Use in pregnancy

Only forms of progesterone that are indicated on product labeling for pregnancy should be used. Some forms of progesterone should not be used in pregnancy Label, 22. Refer to individual product monographs for information regarding use in pregnancy. Many studies have found no effects on fetal development associated with long-term use of contraceptive doses of oral progestins. Studies of infant growth and development that have been conducted have not demonstrated significant adverse effects, however, these studies are few in number. It is therefore advisable to rule out suspected pregnancy before starting any hormonal contraceptive 22.

Effects on fertility

Progesterone at high doses is an antifertility drug and high doses would be expected to impair fertility until cessation 25. The progesterone contraceptive should not be used during pregnancy.

Carcinogenicity

Progesterone has been shown to induce or promote the formation of ovarian, uterine, mammary, and genital tract tumors in animals. The clinical relevance of these findings is unknown 24. Certain epidemiological studies of patients using oral contraceptives have reported an increased relative risk of developing breast cancer, especially at a younger age and associated with a longer duration of use. These studies have mainly involved combined oral contraceptives, and therefore, it is unknown whether this risk is attributable to progestins, estrogens, or a combination of both. At this time, there is insufficient data to determine whether the use of progestin-only contraceptives increases the risk in a similar way to combined contraceptives. A meta-analysis of 54 studies showed a small increase in the frequency of breast cancer diagnosis for women who were currently using combined oral contraceptives, or had used them within the past 10 years. There was no increase in the frequency of having breast cancer diagnosed ten or more years after cessation of hormone use. Women with breast cancer should not use oral contraceptives, as there is no sufficient data to fully establish or negate the risk of cancer with hormonal contraceptive use 22.

Use in breastfeeding

Progesterone has been detected in the milk of nursing mothers 21, 22. No adverse effects, in general, have been found on breastfeeding ability or on the health, growth, or development of the growing infant. Despite this, isolated post-marketing cases of decreased milk production have been reported 22.

Pathways
PathwayCategory
Congenital Lipoid Adrenal Hyperplasia (CLAH) or Lipoid CAHDisease
11-beta-Hydroxylase Deficiency (CYP11B1)Disease
Apparent Mineralocorticoid Excess SyndromeDisease
Adrenal Hyperplasia Type 5 or Congenital Adrenal Hyperplasia Due to 17 alpha-Hydroxylase DeficiencyDisease
Corticosterone Methyl Oxidase I Deficiency (CMO I)Disease
3-beta-Hydroxysteroid Dehydrogenase DeficiencyDisease
SteroidogenesisMetabolic
Adrenal Hyperplasia Type 3 or Congenital Adrenal Hyperplasia Due to 21-Hydroxylase DeficiencyDisease
17-alpha-Hydroxylase Deficiency (CYP17)Disease
21-Hydroxylase Deficiency (CYP21)Disease
Corticosterone Methyl Oxidase II Deficiency (CMO II)Disease
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Progesterone can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Progesterone can be increased when combined with Abatacept.
AbciximabThe therapeutic efficacy of Abciximab can be decreased when used in combination with Progesterone.
AbemaciclibProgesterone may decrease the excretion rate of Abemaciclib which could result in a higher serum level.
AbirateroneThe metabolism of Progesterone can be decreased when combined with Abiraterone.
Food Interactions
  • Administer vitamin supplements.
  • Avoid alcohol.
  • Limit caffeine intake.
  • Take at the same time every day.
  • Take with food.

Products

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Product Images
International/Other Brands
Agolutin (Biotika) / Cyclogest (Actavis) / Gesterol / Gestone (Nordic Pharma) / Progestasert / Progestogel (Besins) / Qi Ning (Aisheng Pharmaceutical) / Relantan (Aversi) / Susten (Sun Pharma) / Utrogestran (Faran Laboratories) / Utrovin (Bestochem) / Vasclor (Verisfield)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Act Progesterone InjectionSolution50 mg / mLIntramuscularTeva Italia S.R.L.2016-04-13Not applicableCanada flag
CrinoneGel90 mg/1.125gVaginalColumbia Laboratories1997-05-13Not applicableUS flag
CrinoneGel90 mg/1.125gVaginalAllergan, Inc.1997-05-13Not applicableUS flag
CrinoneGel45 mg/1.125gVaginalActavis Pharma, Inc.1997-05-132020-02-29US flag
CrinoneGel45 mg/1.125gVaginalAllergan, Inc.1997-05-13Not applicableUS flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Ach-progesteroneCapsule100 mgOralAccord Healthcare, S.L.U.Not applicableNot applicableCanada flag
Auro-progesteroneCapsule100 mgOralAuro Pharma Inc2020-03-16Not applicableCanada flag
PMS-progesteroneCapsule100 mgOralPharmascience Inc2018-08-08Not applicableCanada flag
PMS-progesteroneCapsule200 mgOralPharmascience Inc2019-02-07Not applicableCanada flag
PMS-progesterone Inj 50mg/ml USPLiquid50 mg / mLIntramuscularPharmascience Inc1989-12-312004-01-21Canada flag
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Advanced Formula Progesto-LifeCream16.9 mg/1mLTopicalSmoky Mountain Naturals, LLC - DBA SMNutrition2022-04-01Not applicableUS flag
P25 Progesterone CreamCream25 mg/85gTransdermalSHYNE BRANDS2021-06-10Not applicableUS flag
P50 Progesterone CreamCream1 mg/1mgTransdermalSHYNE BRANDS2021-06-14Not applicableUS flag
P75 Lav Progesterone CreamCream1 mg/1mgTransdermalSHYNE BRANDS2021-06-10Not applicableUS flag
P75 Maxx with Retinol All Natural Progesterone 75 CreamCream1 mg/1mgTransdermalSHYNE BRANDS2021-06-10Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
BijuvaProgesterone (100 mg/1) + Estradiol (0.5 mg/1)CapsuleOralMayne Pharma Inc.2023-03-31Not applicableUS flag
BijuvaProgesterone (100 mg) + Estradiol hemihydrate (0.5 mg)CapsuleOralKnight Therapeutics Inc.Not applicableNot applicableCanada flag
BijuvaProgesterone (100 mg/1) + Estradiol (1 mg/1)CapsuleOralMayne Pharma Inc.2023-12-18Not applicableUS flag
BijuvaProgesterone (100 mg/1) + Estradiol (1 mg/1)CapsuleOralMayne Pharma Inc.2019-04-03Not applicableUS flag
BijuvaProgesterone (100 mg/1) + Estradiol (0.5 mg/1)CapsuleOralMayne Pharma Inc.2023-12-01Not applicableUS flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Advanced Formula Progesto-LifeProgesterone (16.9 mg/1mL)CreamTopicalSmoky Mountain Naturals, LLC - DBA SMNutrition2022-04-01Not applicableUS flag
Fluocinolone Acetonide 0.01% / Minoxidil 7% / Progesterone 0.1%Progesterone (0.1 g/100g) + Fluocinolone acetonide (0.01 g/100g) + Minoxidil (7 g/100g)SolutionTopicalSincerus Florida, LLC2019-05-09Not applicableUS flag
Minoxidil 5% / Progesterone 0.1% / Tretinoin 0.025%Progesterone (0.1 g/100g) + Minoxidil (5 g/100g) + Tretinoin (0.025 g/100g)SolutionTopicalSincerus Florida, LLC2019-05-07Not applicableUS flag
Minoxidil 7% / Progesterone 0.1%Progesterone (0.1 g/100g) + Minoxidil (7 g/100g)SolutionTopicalSincerus Florida, LLC2019-05-01Not applicableUS flag
Minoxidil 7% / Progesterone 0.1% / Tretinoin 0.025%Progesterone (0.1 g/100g) + Minoxidil (7 g/100g) + Tretinoin (0.025 g/100g)SolutionTopicalSincerus Florida, LLC2019-05-07Not applicableUS flag

Categories

ATC Codes
G03FA04 — Progesterone and estrogenG03DA04 — Progesterone
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as gluco/mineralocorticoids, progestogins and derivatives. These are steroids with a structure based on a hydroxylated prostane moiety.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Pregnane steroids
Direct Parent
Gluco/mineralocorticoids, progestogins and derivatives
Alternative Parents
20-oxosteroids / 3-oxo delta-4-steroids / Delta-4-steroids / Cyclohexenones / Organic oxides / Hydrocarbon derivatives
Substituents
20-oxosteroid / 3-oxo-delta-4-steroid / 3-oxosteroid / Aliphatic homopolycyclic compound / Carbonyl group / Cyclic ketone / Cyclohexenone / Delta-4-steroid / Hydrocarbon derivative / Ketone
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
3-oxo Delta(4)-steroid, 20-oxo steroid, C21-steroid hormone (CHEBI:17026) / Pregnane and derivatives [Fig], Progestagens (C00410) / C21 steroids (gluco/mineralocorticoids, progestogins) and derivatives (LMST02030159)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
4G7DS2Q64Y
CAS number
57-83-0
InChI Key
RJKFOVLPORLFTN-LEKSSAKUSA-N
InChI
InChI=1S/C21H30O2/c1-13(22)17-6-7-18-16-5-4-14-12-15(23)8-10-20(14,2)19(16)9-11-21(17,18)3/h12,16-19H,4-11H2,1-3H3/t16-,17+,18-,19-,20-,21+/m0/s1
IUPAC Name
(1S,3aS,3bS,9aR,9bS,11aS)-1-acetyl-9a,11a-dimethyl-1H,2H,3H,3aH,3bH,4H,5H,7H,8H,9H,9aH,9bH,10H,11H,11aH-cyclopenta[a]phenanthren-7-one
SMILES
[H][C@@]12CC[C@H](C(C)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C

References

Synthesis Reference

Nejib M. Nasraoui, Alain Piasco, "Derivatives of 19-nor progesterone; process for producing them and the pharmaceutical compositions incorporating them." U.S. Patent US5223492, issued May, 1971.

US5223492
General References
  1. Allen WM: THE ISOLATION OF CRYSTALLINE PROGESTIN. Science. 1935 Aug 2;82(2118):89-93. [Article]
  2. Allen WM: Progesterone: how did the name originate? South Med J. 1970 Oct;63(10):1151-5. [Article]
  3. Schumacher M, Guennoun R, Robert F, Carelli C, Gago N, Ghoumari A, Gonzalez Deniselle MC, Gonzalez SL, Ibanez C, Labombarda F, Coirini H, Baulieu EE, De Nicola AF: Local synthesis and dual actions of progesterone in the nervous system: neuroprotection and myelination. Growth Horm IGF Res. 2004 Jun;14 Suppl A:S18-33. [Article]
  4. Hould FS, Fried GM, Fazekas AG, Tremblay S, Mersereau WA: Progesterone receptors regulate gallbladder motility. J Surg Res. 1988 Dec;45(6):505-12. [Article]
  5. Payne VA, Chang YT, Loew GH: Homology modeling and substrate binding study of human CYP2C18 and CYP2C19 enzymes. Proteins. 1999 Nov 1;37(2):204-17. [Article]
  6. Yamazaki H, Shimada T: Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9. doi: 10.1006/abbi.1997.0302. [Article]
  7. Young SL, Lessey BA: Progesterone function in human endometrium: clinical perspectives. Semin Reprod Med. 2010 Jan;28(1):5-16. doi: 10.1055/s-0029-1242988. Epub 2010 Jan 26. [Article]
  8. Lopez LM, Ramesh S, Chen M, Edelman A, Otterness C, Trussell J, Helmerhorst FM: Progestin-only contraceptives: effects on weight. Cochrane Database Syst Rev. 2016 Aug 28;(8):CD008815. doi: 10.1002/14651858.CD008815.pub4. [Article]
  9. Khandelwal M: Vaginal progesterone in risk reduction of preterm birth in women with short cervix in the midtrimester of pregnancy. Int J Womens Health. 2012;4:481-90. doi: 10.2147/IJWH.S28944. Epub 2012 Sep 14. [Article]
  10. Okada H, Tsuzuki T, Murata H: Decidualization of the human endometrium. Reprod Med Biol. 2018 Feb 1;17(3):220-227. doi: 10.1002/rmb2.12088. eCollection 2018 Jul. [Article]
  11. Paulson RJ, Collins MG, Yankov VI: Progesterone pharmacokinetics and pharmacodynamics with 3 dosages and 2 regimens of an effervescent micronized progesterone vaginal insert. J Clin Endocrinol Metab. 2014 Nov;99(11):4241-9. doi: 10.1210/jc.2013-3937. Epub 2014 Feb 25. [Article]
  12. Child T, Leonard SA, Evans JS, Lass A: Systematic review of the clinical efficacy of vaginal progesterone for luteal phase support in assisted reproductive technology cycles. Reprod Biomed Online. 2018 Jun;36(6):630-645. doi: 10.1016/j.rbmo.2018.02.001. Epub 2018 Feb 22. [Article]
  13. Check JH: Luteal Phase Support in assisted reproductive technology treatment: focus on Endometrin(R) (progesterone) vaginal insert. Ther Clin Risk Manag. 2009 Aug;5(4):403-7. Epub 2009 Jun 4. [Article]
  14. Grimm SL, Hartig SM, Edwards DP: Progesterone Receptor Signaling Mechanisms. J Mol Biol. 2016 Sep 25;428(19):3831-49. doi: 10.1016/j.jmb.2016.06.020. Epub 2016 Jul 2. [Article]
  15. Danielle B. Cooper; Rotimi Adigun (2018). Oral contraceptives. StatPearls Publishing.
  16. Dhanalakshmi K. Thiyagarajan; Rebecca Jeanmonod (2019). Physiology, Menstrual Cycle. StatPearls publishing.
  17. Drug approval package FDA [Link]
  18. Merck Manuals: Abnormal Uterine Bleeding Due to Ovulatory Dysfunction (AUB-O) [Link]
  19. AAFP: Abnormal uterine bleeding [Link]
  20. Progesterone gel: Crinone® 4% and Crinone® 8% [File]
  21. Endometrin FDA label, vaginal insert [File]
  22. Norethindrone FDA label [File]
  23. Progesterone injection, FDA label [File]
  24. Utrogestan capsules, medsafe NZ label [File]
  25. PROGESTERONE INJECTION USP IN SESAME OIL FOR INTRAMUSCULAR USE ONLY [File]
Human Metabolome Database
HMDB0001830
KEGG Drug
D00066
KEGG Compound
C00410
PubChem Compound
5994
PubChem Substance
46508968
ChemSpider
5773
BindingDB
8903
RxNav
8727
ChEBI
17026
ChEMBL
CHEMBL103
ZINC
ZINC000004428529
Therapeutic Targets Database
DAP000549
PharmGKB
PA451123
PDBe Ligand
STR
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Progesterone
PDB Entries
1a28 / 1dbb / 1h60 / 1mrq / 1w0f / 1ya3 / 2aa5 / 2aa6 / 2aba / 2hzq
show 24 more
FDA label
Download (266 KB)
MSDS
Download (24 KB)

Clinical Trials

Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
Not AvailableActive Not RecruitingBasic ScienceHyperandrogenemia / Polycystic Ovarian Syndrome (PCOS)1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableAutoimmune Disorder / Infertility1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableDementia1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableFemale Infertility / Frozen-thawed Embryo Transfers / Infertility1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableFrozen Embryo Pregnancy Rate1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
  • Bristol myers squibb
  • Amarin pharmaceuticals inc
  • Solvay pharmaceuticals
  • Esi pharmacal
  • Unimed pharmaceuticals llc
  • Watson laboratories inc
  • App pharmaceuticals llc
  • Eli lilly and co
  • Pharmaforce inc
  • Alza corp
  • Ferring pharmaceuticals inc
Packagers
  • Abraxis BioScience Inc.
  • APP Pharmaceuticals
  • Ascend Therapeutics
  • Carlisle Laboratories Inc.
  • Catalent Pharma Solutions
  • Columbia Labs
  • Consolidated Midland Corp.
  • Cutis Pharma Inc.
  • Darby Dental Supply Co. Inc.
  • Fleet Laboratories Ltd.
  • Lyne Laboratories Inc.
  • Marlex Pharmaceuticals
  • Martica Enterprises Inc.
  • Martin Surgical Supply
  • Merit Pharmaceuticals
  • My Healthcare Packaging Ltd. Contract Packaging
  • Paddock Labs
  • Pharmaceutics International Inc.
  • Pharmaforce Inc.
  • Physicians Total Care Inc.
  • Primedics Laboratories
  • Redpharm Drug
  • Solvay Pharmaceuticals
  • Spectrum Chemicals and Laboratory Products
  • V Sab Medical Labs Inc.
  • Watson Pharmaceuticals
Dosage Forms
FormRouteStrength
SolutionIntramuscular50 mg / mL
CreamTopical16.9 mg/1mL
GelVaginal8.000 g
CapsuleOral
GelCutaneous1.000 g
Cream; gelVaginal
GelVaginal4 %
GelVaginal45 mg/1.125g
GelVaginal8 %
GelVaginal80 MG/G
GelVaginal90 MG
GelVaginal90 mg/1.125g
GelVaginal90.000 mg
GelVaginal8 g
GelVaginal8 % w/w
SolutionIntramuscular50.000 mg
SuppositoryVaginal200 mg
TabletVaginal400 mg
SuppositoryVaginal400 mg
SuppositoryRectal; Vaginal400 mg
GelTopical1.00 g
InjectionIntramuscular
InsertVaginal100 mg/1
InsertVaginal100 mg
TabletVaginal100.000 mg
Tablet, effervescentVaginal100 mg
CreamVaginal2.5 G
InsertVaginal200 MG
Capsule; spray, meteredOral; Transdermal
RingVaginal11 mg/1d
Intrauterine deviceIntrauterine; Vaginal1 g
CapsuleVaginal
CapsuleOral; Vaginal400.000 mg
SolutionIntramuscular100 mg
CapsuleOral; Vaginal100.000 mg
Capsule, liquid filledOral; Vaginal200 mg
Capsule, liquid filledOral; Vaginal100 mg
LiquidIntramuscular50 mg / mL
SolutionSubcutaneous25 mg / 1.112 mL
SuspensionIntramuscular
CapsuleOral; Vaginal200.000 mg
SolutionTopical
SolutionIntramuscular25 mg
Capsule200.000 mg
CreamTransdermal25 mg/85g
CreamTransdermal1 mg/1mg
Injection, powder, for solution
Injection, solution
Injection, solution25 mg
CapsuleOral200 mg
GelCutaneous1.00 g
Gel1.000 g
Injection, solutionParenteral25 mg
Capsule, liquid filledOral400 mg
Drug delivery systemVaginal2.074 g
InjectionIntramuscular
InjectionIntramuscular25 mg/ml
InjectionIntramuscular50 mg/ml
Injection, solutionIntramuscular; Subcutaneous
CapsuleNot applicable200 mg/1
Capsule, liquid filledOral100 mg
SolutionParenteral100 mg
Capsule, liquid filledOral200 mg
Capsule, liquid filledVaginal200 mg
CapsuleNot applicable100 mg/1
Capsule, gelatin coatedNot applicable200 mg/1
Capsule, liquid filledOral100 mg/1
Capsule, liquid filledOral200 mg/1
InjectionIntramuscular50 mg/1
Injection, solutionIntramuscular50 mg/1mL
Injection, solutionIntramuscular
GelTopical1 g
Gel
SolutionIntramuscular25 mg/ml
SolutionIntramuscular50 mg/ml
CapsuleOral100 mg/1
CapsuleOral100 mg
CapsuleOral200 mg/1
CapsuleOral; Vaginal200 MG
Injection, solutionIntramuscular10 MG
Injection, solutionIntramuscular25 MG
Injection, solutionIntramuscular5 MG
Injection, solutionIntramuscular50 mg/ml
Injection, solutionParenteral100 MG/ML
Injection, solutionParenteral50 MG/ML
SuspensionParenteral200 mg
Capsule
CapsuleVaginal
CapsuleVaginal200 mg
Gel90 mg
SolutionIntramuscular
Capsule100 mg
Capsule200 mg
TabletVaginal100 mg
Gel1 %w/w
Prices
Unit descriptionCostUnit
Prochieve 4% Gel (18 Applicators Per Box)160.18USD tube
Crinone 8% Gel (1 Box = 6 Applications)84.26USD box
Prochieve 8% Gel 1.45 gm Tube14.83USD tube
Crinone 8% gel13.61USD g
Prochieve 8% gel12.0USD g
Prochieve 4% gel8.56USD g
Progesterone 50 mg/ml6.6USD ml
Progesterone oil 50 mg/ml vial3.88USD ml
Prometrium 200 mg capsule3.84USD capsule
First-progesterone vgs 400 susuppositoryp3.33USD each
First-progesterone vgs 200 suppository3.15USD each
First-progesterone vgs 100 suppository3.0USD each
First-progesterone vgs 50 suppository2.93USD each
First-progesterone vgs 25 suppository2.88USD each
Prometrium 100 mg capsule1.69USD capsule
Progesterone powder micronized0.74USD g
Progesterone powder milled0.73USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5543150No1996-08-062013-09-15US flag
US7300664No2007-11-272019-11-17US flag
US7320800No2008-01-222019-11-17US flag
US7393543No2008-07-012019-11-17US flag
US9006222No2015-04-142032-11-21US flag
US9114145No2015-08-252032-11-21US flag
US8846649No2014-09-302032-11-21US flag
US9301920No2016-04-052032-11-21US flag
US8846648No2014-09-302032-11-21US flag
US9114146No2015-08-252032-11-21US flag
US8633178No2014-01-212032-11-21US flag
US10052386No2018-08-212032-11-21US flag
US8993548No2015-03-312032-11-21US flag
US8987237No2015-03-242032-11-21US flag
US8993549No2015-03-312032-11-21US flag
US10206932No2019-02-192032-11-21US flag
US10639375No2020-05-052032-11-21US flag
US10548904No2020-02-042029-02-03US flag
US8580293No2013-11-122030-01-21US flag
US10537584No2020-01-212029-02-03US flag
US10675288No2020-06-092032-11-21US flag
US10806740No2020-10-202032-11-21US flag
US11033626No2021-06-152032-11-21US flag
US11103513No2021-08-312032-11-21US flag
US11110099No2021-09-072032-11-21US flag
US11103516No2021-08-312032-11-21US flag
US8933059No2015-01-132032-11-21US flag
US11166963No2021-11-092032-11-21US flag
US11529360No2012-11-212032-11-21US flag
US11793819No2012-11-212032-11-21US flag
US11865179No2012-11-212032-11-21US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)128-132https://www.chemicalbook.com/ChemicalProductProperty_US_CB4224484.aspx
boiling point (°C)394.13°C (rough estimate)https://www.chemicalbook.com/ChemicalProductProperty_US_CB4224484.aspx
water solubility<0.1 g/100 mL at 19 ºChttps://www.chemicalbook.com/ChemicalProductProperty_US_CB4224484.aspx
logP3.87http://www.hmdb.ca/metabolites/HMDB0001830
logS-4.43http://www.hmdb.ca/metabolites/HMDB0001830
pKaStrongest acidic: , Strongest basic: 18.92, -4.8http://www.hmdb.ca/metabolites/HMDB0001830
Predicted Properties
PropertyValueSource
Water Solubility0.00546 mg/mLALOGPS
logP3.58ALOGPS
logP4.15Chemaxon
logS-4.8ALOGPS
pKa (Strongest Acidic)18.47Chemaxon
pKa (Strongest Basic)-4.8Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count2Chemaxon
Hydrogen Donor Count0Chemaxon
Polar Surface Area34.14 Å2Chemaxon
Rotatable Bond Count1Chemaxon
Refractivity92.71 m3·mol-1Chemaxon
Polarizability37.26 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleYesChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.982
Caco-2 permeable+0.7724
P-glycoprotein substrateSubstrate0.5449
P-glycoprotein inhibitor IInhibitor0.8841
P-glycoprotein inhibitor IIInhibitor0.6043
Renal organic cation transporterNon-inhibitor0.6931
CYP450 2C9 substrateNon-substrate0.847
CYP450 2D6 substrateNon-substrate0.8795
CYP450 3A4 substrateSubstrate0.7408
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9533
CYP450 2C19 inhibitorNon-inhibitor0.6514
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8203
Ames testNon AMES toxic0.9626
CarcinogenicityNon-carcinogens0.9151
BiodegradationNot ready biodegradable0.9575
Rat acute toxicity1.8041 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7451
hERG inhibition (predictor II)Non-inhibitor0.7454
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (11.5 KB)
Spectra
SpectrumSpectrum TypeSplash Key
GC-MS Spectrum - GC-MSGC-MSsplash10-0fbc-5910000000-422e38df6de7e8b0a4b7
GC-MS Spectrum - GC-MSGC-MSsplash10-0fbc-5910000000-385f45345742235da8e0
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-000g-1590000000-3ebb52b90c541e38c0b4
GC-MS Spectrum - EI-BGC-MSsplash10-024l-6923000000-639c7405f69825de7f90
GC-MS Spectrum - EI-BGC-MSsplash10-0229-2941000000-1e075d8489b79cf4e34a
GC-MS Spectrum - EI-BGC-MSsplash10-0229-3963000000-f35e3d9faf6b2ee87465
GC-MS Spectrum - GC-MSGC-MSsplash10-0fbc-5910000000-422e38df6de7e8b0a4b7
GC-MS Spectrum - GC-MSGC-MSsplash10-0fbc-5910000000-385f45345742235da8e0
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-0f6x-2910000000-1baafb91a3e0b988caa7
Mass Spectrum (Electron Ionization)MSsplash10-006x-7931000000-f6ad83adccd7e016fa29
MS/MS Spectrum - Quattro_QQQ 10V, PositiveLC-MS/MSsplash10-014i-1009000000-0f8b7c3e6c2265c3889f
MS/MS Spectrum - Quattro_QQQ 25V, PositiveLC-MS/MSsplash10-052b-8900000000-0b0167121b798e7e7534
MS/MS Spectrum - Quattro_QQQ 40V, PositiveLC-MS/MSsplash10-052b-9400000000-881510cbcecd9cb61f4f
MS/MS Spectrum - EI-B (JEOL JMS-01-SG-2) , PositiveLC-MS/MSsplash10-024l-6923000000-639c7405f69825de7f90
MS/MS Spectrum - EI-B (HITACHI M-52) , PositiveLC-MS/MSsplash10-0229-2941000000-1e075d8489b79cf4e34a
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-004i-0950000000-ca28d8dfdf780c201716
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-000i-1900000000-857f6720dd17fb2547d1
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-004i-3930000000-fda87095285a83b85ad5
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00kb-7955000000-a22f06eac940cd4f753d
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-014i-0139000000-6b47f75a44df3e20fa3b
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0aba-0950000000-b26d04d179294aa67cc7
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0aba-0920000000-d0a3365efe1f8a589564
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-05aj-0910000000-61d7a07e6be85600e1f1
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-014i-0009000000-67c6f0147801f0ece957
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-05mk-8956000000-aa5fe992c41261b62fbf
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-052b-6910000000-5e26497eb2d0150a30ac
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4j-8900000000-7ca6fd15f0ccc18bfa31
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-052b-9700000000-523fe1ad11bfcbb46f85
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-054k-9400000000-e3d581bd8685e1d3f35d
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4j-5900000000-8a409fe2508f58822f8a
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4j-8900000000-fc9280df2a7dee451abb
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0002-0290000000-0f9dd31ff254325dd522
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0002-0290000000-b59a04537c8d112aa2ab
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-0002-0190000000-b5fed26f17626a75c34c
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-0002-0190000000-58920a9d93488054d8d5
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-002k-0190000000-5f1ba0db62e0ade93f30
MS/MS Spectrum - , positiveLC-MS/MSsplash10-014i-0229000000-c83c60bdf0d3b91077c9
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4j-5921000000-fccf432e6f84ed354acd
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-4921100000-41abb61d58cd1d7a0f7c
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-00kb-0496000000-9d32ec645400bae238ae
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-03di-0009000000-0af9fe9dbb70096e067e
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-03dj-0079000000-b26a1063e643392710a8
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0101-0951000000-d2bf38ea3f5bc713f0db
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-01p9-0093000000-ca47d1a54aac439e3143
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0adl-1920000000-ff0f04d9a59ab28bfab4
1H NMR Spectrum1D NMRNot Applicable
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable
[1H,13C] 2D NMR Spectrum2D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-187.3581755
predicted
DarkChem Lite v0.1.0
[M-H]-187.8123755
predicted
DarkChem Lite v0.1.0
[M-H]-187.8051755
predicted
DarkChem Lite v0.1.0
[M-H]-186.7997755
predicted
DarkChem Lite v0.1.0
[M-H]-187.0225755
predicted
DarkChem Lite v0.1.0
[M-H]-180.22621
predicted
DeepCCS 1.0 (2019)
[M+H]+188.3041755
predicted
DarkChem Lite v0.1.0
[M+H]+175.99825
predicted
DarkChem Standard v0.1.0
[M+H]+189.1595755
predicted
DarkChem Lite v0.1.0
[M+H]+187.3317755
predicted
DarkChem Lite v0.1.0
[M+H]+187.5244755
predicted
DarkChem Lite v0.1.0
[M+H]+182.30602
predicted
DeepCCS 1.0 (2019)
[M+Na]+188.2207755
predicted
DarkChem Lite v0.1.0
[M+Na]+187.9469755
predicted
DarkChem Lite v0.1.0
[M+Na]+188.6825755
predicted
DarkChem Lite v0.1.0
[M+Na]+187.4057755
predicted
DarkChem Lite v0.1.0
[M+Na]+187.1997755
predicted
DarkChem Lite v0.1.0
[M+Na]+188.95586
predicted
DeepCCS 1.0 (2019)

Targets

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Details
1. Progesterone receptor
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Depending on the isoform, progesterone receptor functions as a transcriptional activator or repressor
Specific Function
ATPase binding
Gene Name
PGR
Uniprot ID
P06401
Uniprot Name
Progesterone receptor
Molecular Weight
98979.96 Da
References
  1. Madauss KP, Stewart EL, Williams SP: The evolution of progesterone receptor ligands. Med Res Rev. 2007 May;27(3):374-400. [Article]
  2. Gizard F, Robillard R, Gross B, Barbier O, Revillion F, Peyrat JP, Torpier G, Hum DW, Staels B: TReP-132 is a novel progesterone receptor coactivator required for the inhibition of breast cancer cell growth and enhancement of differentiation by progesterone. Mol Cell Biol. 2006 Oct;26(20):7632-44. [Article]
  3. Boonyaratanakornkit V, McGowan E, Sherman L, Mancini MA, Cheskis BJ, Edwards DP: The role of extranuclear signaling actions of progesterone receptor in mediating progesterone regulation of gene expression and the cell cycle. Mol Endocrinol. 2007 Feb;21(2):359-75. Epub 2006 Nov 30. [Article]
  4. Tranguch S, Smith DF, Dey SK: Progesterone receptor requires a co-chaperone for signalling in uterine biology and implantation. Reprod Biomed Online. 2006 Nov;13(5):651-60. [Article]
  5. Luconi M, Bonaccorsi L, Maggi M, Pecchioli P, Krausz C, Forti G, Baldi E: Identification and characterization of functional nongenomic progesterone receptors on human sperm membrane. J Clin Endocrinol Metab. 1998 Mar;83(3):877-85. [Article]
  6. Okada H, Tsuzuki T, Murata H: Decidualization of the human endometrium. Reprod Med Biol. 2018 Feb 1;17(3):220-227. doi: 10.1002/rmb2.12088. eCollection 2018 Jul. [Article]
  7. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
Agonist
General Function
Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels
Specific Function
DNA-binding transcription factor activity
Gene Name
NR3C2
Uniprot ID
P08235
Uniprot Name
Mineralocorticoid receptor
Molecular Weight
107080.615 Da
References
  1. Rupprecht R, Reul JM, van Steensel B, Spengler D, Soder M, Berning B, Holsboer F, Damm K: Pharmacological and functional characterization of human mineralocorticoid and glucocorticoid receptor ligands. Eur J Pharmacol. 1993 Oct 15;247(2):145-54. [Article]
  2. Quinkler M, Meyer B, Bumke-Vogt C, Grossmann C, Gruber U, Oelkers W, Diederich S, Bahr V: Agonistic and antagonistic properties of progesterone metabolites at the human mineralocorticoid receptor. Eur J Endocrinol. 2002 Jun;146(6):789-99. [Article]
  3. Myles K, Funder JW: Progesterone binding to mineralocorticoid receptors: in vitro and in vivo studies. Am J Physiol. 1996 Apr;270(4 Pt 1):E601-7. doi: 10.1152/ajpendo.1996.270.4.E601. [Article]
  4. Souque A, Fagart J, Couette B, Davioud E, Sobrio F, Marquet A, Rafestin-Oblin ME: The mineralocorticoid activity of progesterone derivatives depends on the nature of the C18 substituent. Endocrinology. 1995 Dec;136(12):5651-8. doi: 10.1210/endo.136.12.7588320. [Article]
Details
3. Estrogen receptor
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
Inhibitor
Downregulator
General Function
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3 (PubMed:17922032). Maintains neuronal survival in response to ischemic reperfusion injury when in the presence of circulating estradiol (17-beta-estradiol/E2) (By similarity)
Specific Function
14-3-3 protein binding
Gene Name
ESR1
Uniprot ID
P03372
Uniprot Name
Estrogen receptor
Molecular Weight
66215.45 Da
References
  1. Lessey BA, Palomino WA, Apparao KB, Young SL, Lininger RA: Estrogen receptor-alpha (ER-alpha) and defects in uterine receptivity in women. Reprod Biol Endocrinol. 2006;4 Suppl 1:S9. [Article]
  2. Montero Girard G, Vanzulli SI, Cerliani JP, Bottino MC, Bolado J, Vela J, Becu-Villalobos D, Benavides F, Gutkind S, Patel V, Molinolo A, Lanari C: Association of estrogen receptor-alpha and progesterone receptor A expression with hormonal mammary carcinogenesis: role of the host microenvironment. Breast Cancer Res. 2007;9(2):R22. [Article]
  3. Mohammed H, Russell IA, Stark R, Rueda OM, Hickey TE, Tarulli GA, Serandour AA, Birrell SN, Bruna A, Saadi A, Menon S, Hadfield J, Pugh M, Raj GV, Brown GD, D'Santos C, Robinson JL, Silva G, Launchbury R, Perou CM, Stingl J, Caldas C, Tilley WD, Carroll JS: Progesterone receptor modulates ERalpha action in breast cancer. Nature. 2015 Jul 16;523(7560):313-7. doi: 10.1038/nature14583. Epub 2015 Jul 8. [Article]
  4. Jayaraman A, Pike CJ: Progesterone attenuates oestrogen neuroprotection via downregulation of oestrogen receptor expression in cultured neurones. J Neuroendocrinol. 2009 Jan;21(1):77-81. doi: 10.1111/j.1365-2826.2008.01801.x. [Article]
  5. Tessier C, Deb S, Prigent-Tessier A, Ferguson-Gottschall S, Gibori GB, Shiu RP, Gibori G: Estrogen receptors alpha and beta in rat decidua cells: cell-specific expression and differential regulation by steroid hormones and prolactin. Endocrinology. 2000 Oct;141(10):3842-51. doi: 10.1210/endo.141.10.7734. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in corticoid and androgen biosynthesis (PubMed:22266943, PubMed:25301938, PubMed:27339894, PubMed:9452426). Catalyzes 17-alpha hydroxylation of C21 steroids, which is common for both pathways. A second oxidative step, required only for androgen synthesis, involves an acyl-carbon cleavage. The 17-alpha hydroxy intermediates, as part of adrenal glucocorticoids biosynthesis pathway, are precursors of cortisol (Probable) (PubMed:25301938, PubMed:9452426). Hydroxylates steroid hormones, pregnenolone and progesterone to form 17-alpha hydroxy metabolites, followed by the cleavage of the C17-C20 bond to form C19 steroids, dehydroepiandrosterone (DHEA) and androstenedione (PubMed:22266943, PubMed:25301938, PubMed:27339894, PubMed:36640554, PubMed:9452426). Has 16-alpha hydroxylase activity. Catalyzes 16-alpha hydroxylation of 17-alpha hydroxy pregnenolone, followed by the cleavage of the C17-C20 bond to form 16-alpha-hydroxy DHEA (PubMed:36640554). Also 16-alpha hydroxylates androgens, relevant for estriol synthesis (PubMed:25301938, PubMed:27339894). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:22266943, PubMed:25301938, PubMed:27339894, PubMed:9452426)
Specific Function
heme binding
Gene Name
CYP17A1
Uniprot ID
P05093
Uniprot Name
Steroid 17-alpha-hydroxylase/17,20 lyase
Molecular Weight
57369.995 Da
References
  1. Haidar S, Hartmann RW: C16 and C17 substituted derivatives of pregnenolone and progesterone as inhibitors of 17alpha-hydroxylase-C17, 20-lyase: synthesis and biological evaluation. Arch Pharm (Weinheim). 2002;335(11-12):526-34. [Article]
  2. Vasaitis TS, Bruno RD, Njar VC: CYP17 inhibitors for prostate cancer therapy. J Steroid Biochem Mol Biol. 2011 May;125(1-2):23-31. doi: 10.1016/j.jsbmb.2010.11.005. Epub 2010 Nov 17. [Article]
  3. Auchus RJ, Sampath Kumar A, Andrew Boswell C, Gupta MK, Bruce K, Rath NP, Covey DF: The enantiomer of progesterone (ent-progesterone) is a competitive inhibitor of human cytochromes P450c17 and P450c21. Arch Biochem Biophys. 2003 Jan 1;409(1):134-44. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Activator
Potentiator
General Function
G-protein coupled opioid receptor that functions as a receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as a receptor for various synthetic opioids and for the psychoactive diterpene salvinorin A. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain. Plays a role in mediating reduced physical activity upon treatment with synthetic opioids. Plays a role in the regulation of salivation in response to synthetic opioids. May play a role in arousal and regulation of autonomic and neuroendocrine functions
Specific Function
dynorphin receptor activity
Gene Name
OPRK1
Uniprot ID
P41145
Uniprot Name
Kappa-type opioid receptor
Molecular Weight
42644.665 Da
References
  1. Dawson-Basoa ME, Gintzler AR: Estrogen and progesterone activate spinal kappa-opiate receptor analgesic mechanisms. Pain. 1996 Jan;64(1):169-77. [Article]
  2. Gordon FT, Soliman MR: The effects of estradiol and progesterone on pain sensitivity and brain opioid receptors in ovariectomized rats. Horm Behav. 1996 Sep;30(3):244-50. doi: 10.1006/hbeh.1996.0029. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction
Specific Function
Not Available
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23539.43 Da
References
  1. Albani JR: Progesterone binding to the tryptophan residues of human alpha1-acid glycoprotein. Carbohydr Res. 2006 Nov 6;341(15):2557-64. Epub 2006 Aug 8. [Article]
  2. De Ceukeleire M, Albani JR: Interaction between carbohydrate residues of alpha(1)-acid glycoprotein (orosomucoid) and progesterone. A fluorescence study. Carbohydr Res. 2002 Sep 3;337(15):1405-10. [Article]
  3. Albani JR: Binding effect of progesterone on the dynamics of alpha1-acid glycoprotein. Biochim Biophys Acta. 1997 Aug 29;1336(2):349-59. [Article]
  4. Nishi K, Sakai N, Komine Y, Maruyama T, Halsall HB, Otagiri M: Structural and drug-binding properties of alpha(1)-acid glycoprotein in reverse micelles. Biochim Biophys Acta. 2002 Dec 16;1601(2):185-91. [Article]
Details
7. Glucocorticoid receptor
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Partial agonist
General Function
Receptor for glucocorticoids (GC) (PubMed:27120390, PubMed:37478846). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors (PubMed:28139699). Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Involved in chromatin remodeling (PubMed:9590696). Plays a role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs and interacting with PNRC2 in a ligand-dependent manner which recruits the RNA helicase UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay (PubMed:25775514). Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth (By similarity)
Specific Function
core promoter sequence-specific DNA binding
Gene Name
NR3C1
Uniprot ID
P04150
Uniprot Name
Glucocorticoid receptor
Molecular Weight
85658.57 Da
References
  1. Attardi BJ, Zeleznik A, Simhan H, Chiao JP, Mattison DR, Caritis SN: Comparison of progesterone and glucocorticoid receptor binding and stimulation of gene expression by progesterone, 17-alpha hydroxyprogesterone caproate, and related progestins. Am J Obstet Gynecol. 2007 Dec;197(6):599.e1-7. [Article]
  2. Xu XF, Hoebeke J, Bjorntorp P: Progestin binds to the glucocorticoid receptor and mediates antiglucocorticoid effect in rat adipose precursor cells. J Steroid Biochem. 1990 Aug 14;36(5):465-71. [Article]
  3. Leo JC, Guo C, Woon CT, Aw SE, Lin VC: Glucocorticoid and mineralocorticoid cross-talk with progesterone receptor to induce focal adhesion and growth inhibition in breast cancer cells. Endocrinology. 2004 Mar;145(3):1314-21. doi: 10.1210/en.2003-0732. Epub 2003 Nov 14. [Article]
Details
8. Androgen receptor
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
Potentiator
General Function
Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849). Transcription factor activity is modulated by bound coactivator and corepressor proteins like ZBTB7A that recruits NCOR1 and NCOR2 to the androgen response elements/ARE on target genes, negatively regulating androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024). Transcription activation is also down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3
Specific Function
androgen binding
Gene Name
AR
Uniprot ID
P10275
Uniprot Name
Androgen receptor
Molecular Weight
99187.115 Da
References
  1. Miedema BW, Kelly KA, Camilleri M, Hanson RB, Zinsmeister AR, O'Connor MK, Brown ML: Human gastric and jejunal transit and motility after Roux gastrojejunostomy. Gastroenterology. 1992 Oct;103(4):1133-43. [Article]
  2. Bentel JM, Birrell SN, Pickering MA, Holds DJ, Horsfall DJ, Tilley WD: Androgen receptor agonist activity of the synthetic progestin, medroxyprogesterone acetate, in human breast cancer cells. Mol Cell Endocrinol. 1999 Aug 20;154(1-2):11-20. [Article]
  3. Yuan X, Balk SP: Mechanisms mediating androgen receptor reactivation after castration. Urol Oncol. 2009 Jan-Feb;27(1):36-41. doi: 10.1016/j.urolonc.2008.03.021. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
Potentiator
General Function
Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone, and 17-beta-estradiol. Regulates the plasma metabolic clearance rate of steroid hormones by controlling their plasma concentration
Specific Function
androgen binding
Gene Name
SHBG
Uniprot ID
P04278
Uniprot Name
Sex hormone-binding globulin
Molecular Weight
43778.755 Da
References
  1. Hong H, Branham WS, Ng HW, Moland CL, Dial SL, Fang H, Perkins R, Sheehan D, Tong W: Human sex hormone-binding globulin binding affinities of 125 structurally diverse chemicals and comparison with their binding to androgen receptor, estrogen receptor, and alpha-fetoprotein. Toxicol Sci. 2015 Feb;143(2):333-48. doi: 10.1093/toxsci/kfu231. Epub 2014 Oct 27. [Article]
  2. Dalton ME: The effect of progesterone administration on sex hormone binding globulin binding capacity in women with severe premenstrual syndrome. J Steroid Biochem. 1984 Jan;20(1):437-9. [Article]
  3. Misao R, Nakanishi Y, Fujimoto J, Tamaya T: Effects of danazol and progesterone on sex hormone-binding globulin mRNA expression in human endometrial cancer cell line Ishikawa. J Steroid Biochem Mol Biol. 1997 Jul;62(4):321-5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
Downregulator
General Function
Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1/ER-alpha, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner (PubMed:20074560)
Specific Function
DNA binding
Gene Name
ESR2
Uniprot ID
Q92731
Uniprot Name
Estrogen receptor beta
Molecular Weight
59215.765 Da
References
  1. Aguirre C, Jayaraman A, Pike C, Baudry M: Progesterone inhibits estrogen-mediated neuroprotection against excitotoxicity by down-regulating estrogen receptor-beta. J Neurochem. 2010 Dec;115(5):1277-87. doi: 10.1111/j.1471-4159.2010.07038.x. Epub 2010 Oct 26. [Article]
  2. Jayaraman A, Pike CJ: Progesterone attenuates oestrogen neuroprotection via downregulation of oestrogen receptor expression in cultured neurones. J Neuroendocrinol. 2009 Jan;21(1):77-81. doi: 10.1111/j.1365-2826.2008.01801.x. [Article]
  3. Tessier C, Deb S, Prigent-Tessier A, Ferguson-Gottschall S, Gibori GB, Shiu RP, Gibori G: Estrogen receptors alpha and beta in rat decidua cells: cell-specific expression and differential regulation by steroid hormones and prolactin. Endocrinology. 2000 Oct;141(10):3842-51. doi: 10.1210/endo.141.10.7734. [Article]
  4. Montero Girard G, Vanzulli SI, Cerliani JP, Bottino MC, Bolado J, Vela J, Becu-Villalobos D, Benavides F, Gutkind S, Patel V, Molinolo A, Lanari C: Association of estrogen receptor-alpha and progesterone receptor A expression with hormonal mammary carcinogenesis: role of the host microenvironment. Breast Cancer Res. 2007;9(2):R22. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in corticoid and androgen biosynthesis (PubMed:22266943, PubMed:25301938, PubMed:27339894, PubMed:9452426). Catalyzes 17-alpha hydroxylation of C21 steroids, which is common for both pathways. A second oxidative step, required only for androgen synthesis, involves an acyl-carbon cleavage. The 17-alpha hydroxy intermediates, as part of adrenal glucocorticoids biosynthesis pathway, are precursors of cortisol (Probable) (PubMed:25301938, PubMed:9452426). Hydroxylates steroid hormones, pregnenolone and progesterone to form 17-alpha hydroxy metabolites, followed by the cleavage of the C17-C20 bond to form C19 steroids, dehydroepiandrosterone (DHEA) and androstenedione (PubMed:22266943, PubMed:25301938, PubMed:27339894, PubMed:36640554, PubMed:9452426). Has 16-alpha hydroxylase activity. Catalyzes 16-alpha hydroxylation of 17-alpha hydroxy pregnenolone, followed by the cleavage of the C17-C20 bond to form 16-alpha-hydroxy DHEA (PubMed:36640554). Also 16-alpha hydroxylates androgens, relevant for estriol synthesis (PubMed:25301938, PubMed:27339894). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:22266943, PubMed:25301938, PubMed:27339894, PubMed:9452426)
Specific Function
heme binding
Gene Name
CYP17A1
Uniprot ID
P05093
Uniprot Name
Steroid 17-alpha-hydroxylase/17,20 lyase
Molecular Weight
57369.995 Da
References
  1. Kossor DC, Kominami S, Takemori S, Colby HD: Role of the steroid 17 alpha-hydroxylase in spironolactone-mediated destruction of adrenal cytochrome P-450. Mol Pharmacol. 1991 Aug;40(2):321-5. [Article]
  2. Kater CE, Biglieri EG: Disorders of steroid 17 alpha-hydroxylase deficiency. Endocrinol Metab Clin North Am. 1994 Jun;23(2):341-57. [Article]
  3. Petrunak EM, DeVore NM, Porubsky PR, Scott EE: Structures of human steroidogenic cytochrome P450 17A1 with substrates. J Biol Chem. 2014 Nov 21;289(47):32952-64. doi: 10.1074/jbc.M114.610998. Epub 2014 Oct 9. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15041462, PubMed:15805301, PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15041462, PubMed:15805301, PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C15-alpha and C16-alpha positions (PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15805301). Displays different regioselectivities for polyunsaturated fatty acids (PUFA) hydroxylation (PubMed:15041462, PubMed:18577768). Catalyzes the epoxidation of double bonds of certain PUFA (PubMed:15041462, PubMed:19965576, PubMed:20972997). Converts arachidonic acid toward epoxyeicosatrienoic acid (EET) regioisomers, 8,9-, 11,12-, and 14,15-EET, that function as lipid mediators in the vascular system (PubMed:20972997). Displays an absolute stereoselectivity in the epoxidation of eicosapentaenoic acid (EPA) producing the 17(R),18(S) enantiomer (PubMed:15041462). May play an important role in all-trans retinoic acid biosynthesis in extrahepatic tissues. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195)
Specific Function
arachidonic acid monooxygenase activity
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
References
  1. Schwarz D, Kisselev P, Schunck WH, Chernogolov A, Boidol W, Cascorbi I, Roots I: Allelic variants of human cytochrome P450 1A1 (CYP1A1): effect of T461N and I462V substitutions on steroid hydroxylase specificity. Pharmacogenetics. 2000 Aug;10(6):519-30. [Article]
  2. Niwa T, Yabusaki Y, Honma K, Matsuo N, Tatsuta K, Ishibashi F, Katagiri M: Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47. doi: 10.1080/004982598239290 . [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:15258110, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:15258110, PubMed:20972997). Exhibits catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2- and 4-hydroxy E1 and E2. Displays a predominant hydroxylase activity toward E2 at the C-4 position (PubMed:11555828, PubMed:12865317). Metabolizes testosterone and progesterone to B or D ring hydroxylated metabolites (PubMed:10426814). May act as a major enzyme for all-trans retinoic acid biosynthesis in extrahepatic tissues. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376, PubMed:15258110). Catalyzes the epoxidation of double bonds of certain PUFA. Converts arachidonic acid toward epoxyeicosatrienoic acid (EpETrE) regioisomers, 8,9-, 11,12-, and 14,15- EpETrE, that function as lipid mediators in the vascular system (PubMed:20972997). Additionally, displays dehydratase activity toward oxygenated eicosanoids hydroperoxyeicosatetraenoates (HpETEs). This activity is independent of cytochrome P450 reductase, NADPH, and O2 (PubMed:21068195). Also involved in the oxidative metabolism of xenobiotics, particularly converting polycyclic aromatic hydrocarbons and heterocyclic aryl amines procarcinogens to DNA-damaging products (PubMed:10426814). Plays an important role in retinal vascular development. Under hyperoxic O2 conditions, promotes retinal angiogenesis and capillary morphogenesis, likely by metabolizing the oxygenated products generated during the oxidative stress. Also, contributes to oxidative homeostasis and ultrastructural organization and function of trabecular meshwork tissue through modulation of POSTN expression (By similarity)
Specific Function
aromatase activity
Gene Name
CYP1B1
Uniprot ID
Q16678
Uniprot Name
Cytochrome P450 1B1
Molecular Weight
60845.33 Da
References
  1. Shimada T, Watanabe J, Kawajiri K, Sutter TR, Guengerich FP, Gillam EM, Inoue K: Catalytic properties of polymorphic human cytochrome P450 1B1 variants. Carcinogenesis. 1999 Aug;20(8):1607-13. doi: 10.1093/carcin/20.8.1607. [Article]
  2. Li F, Zhu W, Gonzalez FJ: Potential role of CYP1B1 in the development and treatment of metabolic diseases. Pharmacol Ther. 2017 Oct;178:18-30. doi: 10.1016/j.pharmthera.2017.03.007. Epub 2017 Mar 16. [Article]
  3. Jansson I, Stoilov I, Sarfarazi M, Schenkman JB: Effect of two mutations of human CYP1B1, G61E and R469W, on stability and endogenous steroid substrate metabolism. Pharmacogenetics. 2001 Dec;11(9):793-801. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity
Specific Function
arachidonic acid epoxygenase activity
Gene Name
CYP2A6
Uniprot ID
P11509
Uniprot Name
Cytochrome P450 2A6
Molecular Weight
56517.005 Da
References
  1. Choi SY, Koh KH, Jeong H: Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9. doi: 10.1124/dmd.112.046276. Epub 2012 Jul 26. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
Specific Function
anandamide 11,12 epoxidase activity
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Niwa T, Hiroi T, Tsuzuki D, Yamamoto S, Narimatsu S, Fukuda T, Azuma J, Funae Y: Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23. doi: 10.1016/j.molbrainres.2004.06.030. [Article]
  2. Niwa T, Okada K, Hiroi T, Imaoka S, Narimatsu S, Funae Y: Effect of psychotropic drugs on the 21-hydroxylation of neurosteroids, progesterone and allopregnanolone, catalyzed by rat CYP2D4 and human CYP2D6 in the brain. Biol Pharm Bull. 2008 Mar;31(3):348-51. [Article]
  3. Miller RT, Miksys S, Hoffmann E, Tyndale RF: Ethanol self-administration and nicotine treatment increase brain levels of CYP2D in African green monkeys. Br J Pharmacol. 2014 Jun;171(12):3077-88. doi: 10.1111/bph.12652. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:20972997). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. Hydroxylates fenbendazole at the 4' position (PubMed:23959307)
Specific Function
(R)-limonene 6-monooxygenase activity
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55944.565 Da
References
  1. Lin Y, Lu P, Tang C, Mei Q, Sandig G, Rodrigues AD, Rushmore TH, Shou M: Substrate inhibition kinetics for cytochrome P450-catalyzed reactions. Drug Metab Dispos. 2001 Apr;29(4 Pt 1):368-74. [Article]
  2. Yamazaki H, Shimada T: Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9. doi: 10.1006/abbi.1997.0302. [Article]
  3. Gomes LG, Huang N, Agrawal V, Mendonca BB, Bachega TA, Miller WL: Extraadrenal 21-hydroxylation by CYP2C19 and CYP3A4: effect on 21-hydroxylase deficiency. J Clin Endocrinol Metab. 2009 Jan;94(1):89-95. doi: 10.1210/jc.2008-1174. Epub 2008 Oct 28. [Article]
  4. Mitsuda M, Iwasaki M, Asahi S: Cynomolgus monkey cytochrome P450 2C43: cDNA cloning, heterologous expression, purification and characterization. J Biochem. 2006 May;139(5):865-72. doi: 10.1093/jb/mvj093. [Article]
  5. Richardson TH, Jung F, Griffin KJ, Wester M, Raucy JL, Kemper B, Bornheim LM, Hassett C, Omiecinski CJ, Johnson EF: A universal approach to the expression of human and rabbit cytochrome P450s of the 2C subfamily in Escherichia coli. Arch Biochem Biophys. 1995 Oct 20;323(1):87-96. doi: 10.1006/abbi.1995.0013. [Article]
Details
7. Cytochrome P450 2C9
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
Specific Function
(R)-limonene 6-monooxygenase activity
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Yamazaki H, Shimada T: Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9. doi: 10.1006/abbi.1997.0302. [Article]
  2. Du H, Wei Z, Yan Y, Xiong Y, Zhang X, Shen L, Ruan Y, Wu X, Xu Q, He L, Qin S: Functional Characterization of Human CYP2C9 Allelic Variants in COS-7 Cells. Front Pharmacol. 2016 Apr 25;7:98. doi: 10.3389/fphar.2016.00098. eCollection 2016. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione (PubMed:2732228). Catalyzes the oxidative conversion of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine (PubMed:2732228)
Specific Function
aromatase activity
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Quinney SK, Benjamin T, Zheng X, Patil AS: Characterization of Maternal and Fetal CYP3A-Mediated Progesterone Metabolism. Fetal Pediatr Pathol. 2017 Oct;36(5):400-411. doi: 10.1080/15513815.2017.1354411. Epub 2017 Sep 26. [Article]
  2. Bustos ML, Caritis SN, Jablonski KA, Reddy UM, Sorokin Y, Manuck T, Varner MW, Wapner RJ, Iams JD, Carpenter MW, Peaceman AM, Mercer BM, Sciscione A, Rouse DJ, Ramin SM: The association among cytochrome P450 3A, progesterone receptor polymorphisms, plasma 17-alpha hydroxyprogesterone caproate concentrations, and spontaneous preterm birth. Am J Obstet Gynecol. 2017 Sep;217(3):369.e1-369.e9. doi: 10.1016/j.ajog.2017.05.019. Epub 2017 May 15. [Article]
  3. CYP3A5 cytochrome P450 family 3 subfamily A member 5 [ Homo sapiens (human) ] [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
Specific Function
1,8-cineole 2-exo-monooxygenase activity
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Jang GR, Wrighton SA, Benet LZ: Identification of CYP3A4 as the principal enzyme catalyzing mifepristone (RU 486) oxidation in human liver microsomes. Biochem Pharmacol. 1996 Sep 13;52(5):753-61. [Article]
  2. Sevrioukova IF, Poulos TL: Understanding the mechanism of cytochrome P450 3A4: recent advances and remaining problems. Dalton Trans. 2013 Mar 7;42(9):3116-26. doi: 10.1039/c2dt31833d. Epub 2012 Sep 27. [Article]
  3. Polic V, Auclair K: Allosteric Activation of Cytochrome P450 3A4 via Progesterone Bioconjugation. Bioconjug Chem. 2017 Apr 19;28(4):885-889. doi: 10.1021/acs.bioconjchem.6b00604. Epub 2017 Mar 29. [Article]
  4. Williams PA, Cosme J, Vinkovic DM, Ward A, Angove HC, Day PJ, Vonrhein C, Tickle IJ, Jhoti H: Crystal structures of human cytochrome P450 3A4 bound to metyrapone and progesterone. Science. 2004 Jul 30;305(5684):683-6. Epub 2004 Jul 15. [Article]
  5. Tsunoda SM, Harris RZ, Mroczkowski PJ, Benet LZ: Preliminary evaluation of progestins as inducers of cytochrome P450 3A4 activity in postmenopausal women. J Clin Pharmacol. 1998 Dec;38(12):1137-43. [Article]
  6. Choi SY, Koh KH, Jeong H: Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9. doi: 10.1124/dmd.112.046276. Epub 2012 Jul 26. [Article]
  7. Prometrium FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
Data are limited to the results of in vitro studies.
General Function
A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins during embryogenesis (PubMed:11093772, PubMed:12865317, PubMed:14559847, PubMed:17178770, PubMed:9555064). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:12865317, PubMed:14559847, PubMed:17178770, PubMed:9555064). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes 3beta-hydroxyandrost-5-en-17-one (dehydroepiandrosterone, DHEA), a precursor in the biosynthesis of androgen and estrogen steroid hormones (PubMed:17178770, PubMed:9555064). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1), particularly D-ring hydroxylated estrone at the C16-alpha position (PubMed:12865317, PubMed:14559847). Mainly hydroxylates all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in atRA clearance during fetal development (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics including anticonvulsants (PubMed:9555064)
Specific Function
all-trans retinoic acid 18-hydroxylase activity
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57469.95 Da
References
  1. Quinney SK, Benjamin T, Zheng X, Patil AS: Characterization of Maternal and Fetal CYP3A-Mediated Progesterone Metabolism. Fetal Pediatr Pathol. 2017 Oct;36(5):400-411. doi: 10.1080/15513815.2017.1354411. Epub 2017 Sep 26. [Article]
  2. Sharma S, Ellis EC, Dorko K, Zhang S, Mattison DR, Caritis SN, Venkataramanan R, Strom SC: Metabolism of 17alpha-hydroxyprogesterone caproate, an agent for preventing preterm birth, by fetal hepatocytes. Drug Metab Dispos. 2010 May;38(5):723-7. doi: 10.1124/dmd.109.029918. Epub 2010 Jan 22. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
General Function
Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
Specific Function
ABC-type xenobiotic transporter activity
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
ATP-dependent translocase ABCB1
Molecular Weight
141477.255 Da
References
  1. Romiti N, Tramonti G, Chieli E: Influence of different chemicals on MDR-1 P-glycoprotein expression and activity in the HK-2 proximal tubular cell line. Toxicol Appl Pharmacol. 2002 Sep 1;183(2):83-91. [Article]
  2. Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. [Article]
  3. Leonessa F, Kim JH, Ghiorghis A, Kulawiec RJ, Hammer C, Talebian A, Clarke R: C-7 analogues of progesterone as potent inhibitors of the P-glycoprotein efflux pump. J Med Chem. 2002 Jan 17;45(2):390-8. [Article]
  4. Ueda K, Okamura N, Hirai M, Tanigawara Y, Saeki T, Kioka N, Komano T, Hori R: Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone. J Biol Chem. 1992 Dec 5;267(34):24248-52. [Article]
  5. Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. [Article]
  6. Yamazaki M, Neway WE, Ohe T, Chen I, Rowe JF, Hochman JH, Chiba M, Lin JH: In vitro substrate identification studies for p-glycoprotein-mediated transport: species difference and predictability of in vivo results. J Pharmacol Exp Ther. 2001 Mar;296(3):723-35. [Article]
  7. Adachi Y, Suzuki H, Sugiyama Y: Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8. [Article]
  8. Borgnia MJ, Eytan GD, Assaraf YG: Competition of hydrophobic peptides, cytotoxic drugs, and chemosensitizers on a common P-glycoprotein pharmacophore as revealed by its ATPase activity. J Biol Chem. 1996 Feb 9;271(6):3163-71. [Article]
  9. Kim WY, Benet LZ: P-glycoprotein (P-gp/MDR1)-mediated efflux of sex-steroid hormones and modulation of P-gp expression in vitro. Pharm Res. 2004 Jul;21(7):1284-93. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:9260930, PubMed:9687576). Functions as a Na(+)-independent, bidirectional uniporter (PubMed:21128598, PubMed:9687576). Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:15212162, PubMed:9260930, PubMed:9687576). However, may also engage electroneutral cation exchange when saturating concentrations of cation substrates are reached (By similarity). Predominantly expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (PubMed:15783073). Implicated in monoamine neurotransmitters uptake such as histamine, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, serotonin and tyramine, thereby supporting a physiological role in the central nervous system by regulating interstitial concentrations of neurotransmitters (PubMed:16581093, PubMed:17460754, PubMed:9687576). Also capable of transporting dopaminergic neuromodulators cyclo(his-pro), salsolinol and N-methyl-salsolinol, thereby involved in the maintenance of dopaminergic cell integrity in the central nervous system (PubMed:17460754). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Also transports guanidine and endogenous monoamines such as vitamin B1/thiamine, creatinine and N-1-methylnicotinamide (NMN) (PubMed:12089365, PubMed:15212162, PubMed:17072098, PubMed:24961373, PubMed:9260930). Mediates the uptake and efflux of quaternary ammonium compound choline (PubMed:9260930). Mediates the bidirectional transport of polyamine agmatine and the uptake of polyamines putrescine and spermidine (PubMed:12538837, PubMed:21128598). Able to transport non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). Also involved in the uptake of xenobiotic 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:12395288, PubMed:16394027). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
Specific Function
acetylcholine transmembrane transporter activity
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
References
  1. Hayer-Zillgen M, Bruss M, Bonisch H: Expression and pharmacological profile of the human organic cation transporters hOCT1, hOCT2 and hOCT3. Br J Pharmacol. 2002 Jul;136(6):829-36. [Article]
  2. Wu X, Kekuda R, Huang W, Fei YJ, Leibach FH, Chen J, Conway SJ, Ganapathy V: Identity of the organic cation transporter OCT3 as the extraneuronal monoamine transporter (uptake2) and evidence for the expression of the transporter in the brain. J Biol Chem. 1998 Dec 4;273(49):32776-86. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:11388889, PubMed:11408531, PubMed:12439218, PubMed:12719534, PubMed:15389554, PubMed:16263091, PubMed:16272756, PubMed:16581093, PubMed:19536068, PubMed:21128598, PubMed:23680637, PubMed:24961373, PubMed:34040533, PubMed:9187257, PubMed:9260930, PubMed:9655880). Functions as a pH- and Na(+)-independent, bidirectional transporter (By similarity). Cation cellular uptake or release is driven by the electrochemical potential (i.e. membrane potential and concentration gradient) and substrate selectivity (By similarity). Hydrophobicity is a major requirement for recognition in polyvalent substrates and inhibitors (By similarity). Primarily expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (By similarity). Most likely functions as an uptake carrier in enterocytes contributing to the intestinal elimination of organic cations from the systemic circulation (PubMed:16263091). Transports endogenous monoamines such as N-1-methylnicotinamide (NMN), guanidine, histamine, neurotransmitters dopamine, serotonin and adrenaline (PubMed:12439218, PubMed:24961373, PubMed:35469921, PubMed:9260930). Also transports natural polyamines such as spermidine, agmatine and putrescine at low affinity, but relatively high turnover (PubMed:21128598). Involved in the hepatic uptake of vitamin B1/thiamine, hence regulating hepatic lipid and energy metabolism (PubMed:24961373). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with lower efficency (PubMed:17460754). Also capable of transporting non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). May contribute to the transport of cationic compounds in testes across the blood-testis-barrier (Probable). Also involved in the uptake of xenobiotics tributylmethylammonium (TBuMA), quinidine, N-methyl-quinine (NMQ), N-methyl-quinidine (NMQD) N-(4,4-azo-n-pentyl)-quinuclidine (APQ), azidoprocainamide methoiodide (AMP), N-(4,4-azo-n-pentyl)-21-deoxyajmalinium (APDA) and 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:11408531, PubMed:15389554, PubMed:35469921, PubMed:9260930)
Specific Function
(R)-carnitine transmembrane transporter activity
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da
References
  1. Hayer-Zillgen M, Bruss M, Bonisch H: Expression and pharmacological profile of the human organic cation transporters hOCT1, hOCT2 and hOCT3. Br J Pharmacol. 2002 Jul;136(6):829-36. [Article]
  2. Wu X, Kekuda R, Huang W, Fei YJ, Leibach FH, Chen J, Conway SJ, Ganapathy V: Identity of the organic cation transporter OCT3 as the extraneuronal monoamine transporter (uptake2) and evidence for the expression of the transporter in the brain. J Biol Chem. 1998 Dec 4;273(49):32776-86. [Article]
  3. Lozano E, Herraez E, Briz O, Robledo VS, Hernandez-Iglesias J, Gonzalez-Hernandez A, Marin JJ: Role of the plasma membrane transporter of organic cations OCT1 and its genetic variants in modern liver pharmacology. Biomed Res Int. 2013;2013:692071. doi: 10.1155/2013/692071. Epub 2013 Jul 31. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:10196521, PubMed:10966924, PubMed:12538837, PubMed:17460754, PubMed:20858707). Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:10966924). Functions as a Na(+)- and Cl(-)-independent, bidirectional uniporter (PubMed:12538837). Implicated in monoamine neurotransmitters uptake such as dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, histamine, serotonin and tyramine, thereby supporting a role in homeostatic regulation of aminergic neurotransmission in the brain (PubMed:10196521, PubMed:16581093, PubMed:20858707). Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with low efficiency (PubMed:17460754). May be involved in the uptake and disposition of cationic compounds by renal clearance from the blood flow (PubMed:10966924). May contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (Probable). Mediates the transport of polyamine spermidine and putrescine (By similarity). Mediates the bidirectional transport of polyamine agmatine (PubMed:12538837). Also transports guanidine (PubMed:10966924). May also mediate intracellular transport of organic cations, thereby playing a role in amine metabolism and intracellular signaling (By similarity)
Specific Function
monoamine transmembrane transporter activity
Gene Name
SLC22A3
Uniprot ID
O75751
Uniprot Name
Solute carrier family 22 member 3
Molecular Weight
61279.485 Da
References
  1. Hayer-Zillgen M, Bruss M, Bonisch H: Expression and pharmacological profile of the human organic cation transporters hOCT1, hOCT2 and hOCT3. Br J Pharmacol. 2002 Jul;136(6):829-36. [Article]
  2. Wu X, Kekuda R, Huang W, Fei YJ, Leibach FH, Chen J, Conway SJ, Ganapathy V: Identity of the organic cation transporter OCT3 as the extraneuronal monoamine transporter (uptake2) and evidence for the expression of the transporter in the brain. J Biol Chem. 1998 Dec 4;273(49):32776-86. [Article]
Details
5. Bile salt export pump
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Catalyzes the transport of the major hydrophobic bile salts, such as taurine and glycine-conjugated cholic acid across the canalicular membrane of hepatocytes in an ATP-dependent manner, therefore participates in hepatic bile acid homeostasis and consequently to lipid homeostasis through regulation of biliary lipid secretion in a bile salts dependent manner (PubMed:15791618, PubMed:16332456, PubMed:18985798, PubMed:19228692, PubMed:20010382, PubMed:20398791, PubMed:22262466, PubMed:24711118, PubMed:29507376, PubMed:32203132). Transports taurine-conjugated bile salts more rapidly than glycine-conjugated bile salts (PubMed:16332456). Also transports non-bile acid compounds, such as pravastatin and fexofenadine in an ATP-dependent manner and may be involved in their biliary excretion (PubMed:15901796, PubMed:18245269)
Specific Function
ABC-type bile acid transporter activity
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Wang EJ, Casciano CN, Clement RP, Johnson WW: Fluorescent substrates of sister-P-glycoprotein (BSEP) evaluated as markers of active transport and inhibition: evidence for contingent unequal binding sites. Pharm Res. 2003 Apr;20(4):537-44. [Article]
  2. Abu-Hayyeh S, Williamson C: Progesterone metabolites as farnesoid X receptor inhibitors. Dig Dis. 2015;33(3):300-6. doi: 10.1159/000371565. Epub 2015 May 27. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Mediates export of organic anions and drugs from the cytoplasm (PubMed:10064732, PubMed:11114332, PubMed:16230346, PubMed:7961706, PubMed:9281595). Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics (PubMed:10064732, PubMed:11114332, PubMed:16230346, PubMed:7961706, PubMed:9281595). Confers resistance to anticancer drugs by decreasing accumulation of drug in cells, and by mediating ATP- and GSH-dependent drug export (PubMed:9281595). Hydrolyzes ATP with low efficiency (PubMed:16230346). Catalyzes the export of sphingosine 1-phosphate from mast cells independently of their degranulation (PubMed:17050692). Participates in inflammatory response by allowing export of leukotriene C4 from leukotriene C4-synthezing cells (By similarity). Mediates ATP-dependent, GSH-independent cyclic GMP-AMP (cGAMP) export (PubMed:36070769). Thus, by limiting intracellular cGAMP concentrations negatively regulates the cGAS-STING pathway (PubMed:36070769)
Specific Function
ABC-type glutathione S-conjugate transporter activity
Gene Name
ABCC1
Uniprot ID
P33527
Uniprot Name
Multidrug resistance-associated protein 1
Molecular Weight
171589.5 Da
References
  1. Payen L, Delugin L, Courtois A, Trinquart Y, Guillouzo A, Fardel O: Reversal of MRP-mediated multidrug resistance in human lung cancer cells by the antiprogestatin drug RU486. Biochem Biophys Res Commun. 1999 May 19;258(3):513-8. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
As a major transporter of conjugated bile salts from plasma into the hepatocyte, it plays a key role in the enterohepatic circulation of bile salts necessary for the solubilization and absorption of dietary fat and fat-soluble vitamins (PubMed:14660639, PubMed:24867799, PubMed:34060352, PubMed:8132774). It is strictly dependent on the extracellular presence of sodium (PubMed:14660639, PubMed:24867799, PubMed:34060352, PubMed:8132774). It exhibits broad substrate specificity and transports various bile acids, such as taurocholate, cholate, as well as non-bile acid organic compounds, such as estrone sulfate (PubMed:14660639, PubMed:34060352). Works collaboratively with the ileal transporter (NTCP2), the organic solute transporter (OST), and the bile salt export pump (BSEP), to ensure efficacious biological recycling of bile acids during enterohepatic circulation (PubMed:33222321)
Specific Function
bile acid
Gene Name
SLC10A1
Uniprot ID
Q14973
Uniprot Name
Hepatic sodium/bile acid cotransporter
Molecular Weight
38118.64 Da
References
  1. Schroeder A, Eckhardt U, Stieger B, Tynes R, Schteingart CD, Hofmann AF, Meier PJ, Hagenbuch B: Substrate specificity of the rat liver Na(+)-bile salt cotransporter in Xenopus laevis oocytes and in CHO cells. Am J Physiol. 1998 Feb;274(2 Pt 1):G370-5. [Article]
  2. Abu-Hayyeh S, Williamson C: Progesterone metabolites as farnesoid X receptor inhibitors. Dig Dis. 2015;33(3):300-6. doi: 10.1159/000371565. Epub 2015 May 27. [Article]
  3. Abu-Hayyeh S, Martinez-Becerra P, Sheikh Abdul Kadir SH, Selden C, Romero MR, Rees M, Marschall HU, Marin JJ, Williamson C: Inhibition of Na+-taurocholate Co-transporting polypeptide-mediated bile acid transport by cholestatic sulfated progesterone metabolites. J Biol Chem. 2010 May 28;285(22):16504-12. doi: 10.1074/jbc.M109.072140. Epub 2010 Feb 20. [Article]
  4. Kim RB, Leake B, Cvetkovic M, Roden MM, Nadeau J, Walubo A, Wilkinson GR: Modulation by drugs of human hepatic sodium-dependent bile acid transporter (sodium taurocholate cotransporting polypeptide) activity. J Pharmacol Exp Ther. 1999 Dec;291(3):1204-9. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Data regarding this transporter activity are limited to in vitro studies.
General Function
Mediates the Na(+)-independent uptake of organic anions (PubMed:10358072, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) (PubMed:10358072, PubMed:10601278, PubMed:10873595, PubMed:11159893, PubMed:12196548, PubMed:12568656, PubMed:15159445, PubMed:15970799, PubMed:16627748, PubMed:17412826, PubMed:19129463, PubMed:26979622). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Involved in the clearance of endogenous and exogenous substrates from the liver (PubMed:10358072, PubMed:10601278). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:10601278, PubMed:15159445, PubMed:15970799). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748). Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463)
Specific Function
bile acid transmembrane transporter activity
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Gui C, Obaidat A, Chaguturu R, Hagenbuch B: Development of a cell-based high-throughput assay to screen for inhibitors of organic anion transporting polypeptides 1B1 and 1B3. Curr Chem Genomics. 2010 Mar 1;4:1-8. doi: 10.2174/1875397301004010001. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
General Function
Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity)
Specific Function
ABC-type xenobiotic transporter activity
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
Broad substrate specificity ATP-binding cassette transporter ABCG2
Molecular Weight
72313.47 Da
References
  1. Mao Q, Unadkat JD: Role of the breast cancer resistance protein (BCRP/ABCG2) in drug transport--an update. AAPS J. 2015 Jan;17(1):65-82. doi: 10.1208/s12248-014-9668-6. Epub 2014 Sep 19. [Article]
  2. Mao Q: BCRP/ABCG2 in the placenta: expression, function and regulation. Pharm Res. 2008 Jun;25(6):1244-55. doi: 10.1007/s11095-008-9537-z. [Article]
  3. Wu X, Zhang X, Sun L, Zhang H, Li L, Wang X, Li W, Su P, Hu J, Gao P, Zhou G: Progesterone negatively regulates BCRP in progesterone receptor-positive human breast cancer cells. Cell Physiol Biochem. 2013;32(2):344-54. doi: 10.1159/000354442. Epub 2013 Aug 14. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Mediates the Na(+)-independent uptake of organic anions (PubMed:10779507, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (17-beta-glucuronosyl estradiol, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate), as well as eicosanoid leukotriene C4, prostaglandin E2 and L-thyroxine (T4) (PubMed:10779507, PubMed:11159893, PubMed:12568656, PubMed:15159445, PubMed:17412826, PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463). Shows a pH-sensitive substrate specificity towards sulfated steroids, taurocholate and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Involved in the clearance of bile acids and organic anions from the liver (PubMed:22232210). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins) such as pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:15159445). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748)
Specific Function
bile acid transmembrane transporter activity
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. Patik I, Szekely V, Nemet O, Szepesi A, Kucsma N, Varady G, Szakacs G, Bakos E, Ozvegy-Laczka C: Identification of novel cell-impermeant fluorescent substrates for testing the function and drug interaction of Organic Anion-Transporting Polypeptides, OATP1B1/1B3 and 2B1. Sci Rep. 2018 Feb 8;8(1):2630. doi: 10.1038/s41598-018-20815-1. [Article]
  2. Gui C, Obaidat A, Chaguturu R, Hagenbuch B: Development of a cell-based high-throughput assay to screen for inhibitors of organic anion transporting polypeptides 1B1 and 1B3. Curr Chem Genomics. 2010 Mar 1;4:1-8. doi: 10.2174/1875397301004010001. [Article]

Drug created at June 13, 2005 13:24 / Updated at October 10, 2024 16:18