Estradiol valerate

Identification

Summary

Estradiol valerate is an estradiol prodrug used to treat some effects of menopause, hypoestrogenism, androgen dependant carcinoma of the prostate, and in combination products for endometriosis and contraception.

Brand Names
Delestrogen, Natazia
Generic Name
Estradiol valerate
DrugBank Accession Number
DB13956
Background

Estradiol Valerate (also known as E2V) is a pro-drug ester of Estradiol, a naturally occurring hormone that circulates endogenously within the human body. Estradiol is the most potent form of all mammalian estrogenic steroids and acts as the major female sex hormone. As a pro-drug of estradiol, estradiol acetate therefore has the same downstream effects within the body through binding to the Estrogen Receptor (ER) including ERα and ERβ subtypes, which are located in various tissues including in the breasts, uterus, ovaries, skin, prostate, bone, fat, and brain.

Estradiol is commonly produced with an ester side-chain as endogenous estradiol has very low oral bioavailability on its own (2-10%). First-pass metabolism by the gut and the liver quickly degrades the estradiol molecule before it gets a chance to enter systemic circulation and exert its estrogenic effects 9. Esterification of estradiol aims to improves absorption and bioavailability after oral administration (such as with Estradiol valerate) or to sustain release from depot intramuscular injections (such as with Estradiol Cypionate) through improved lipophilicity. Following absorption, the esters are cleaved, resulting in the release of endogenous estradiol, or 17β-estradiol. Ester pro-drugs of estradiol are therefore considered to be bioidentical forms of estrogen 12.

Estradiol valerate is commercially available as an intramuscular injection as the product Delestrogen and is indicated for the treatment of moderate to severe vasomotor symptoms and vulvovaginal atrophy due to menopause, for the treatment of hypoestrogenism due to hypogonadism, castration or primary ovarian failure, and for the treatment of advanced androgen-dependent carcinoma of the prostate (for palliation only). Estradiol valerate is also available in combination with Dienogest as the commercially available product Natazia used for the prevention of pregnancy and for the treatment of heavy menstrual bleeding.

The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mcg of estradiol daily, depending on the phase of the menstrual cycle. However, after menopause, most endogenous estrogen is produced by conversion of androstenedione, secreted by the adrenal cortex, to estrone by peripheral tissues. Thus, estrone and the sulfate conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women Label. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol at the receptor level. Because of the difference in potency between estradiol and estrone, menopause (and a change in primary hormone from estradiol to estrone) is associated with a number of symptoms associated with this reduction in potency and in estrogenic effects. These include hot flashes, vaginal dryness, mood changes, irregular menses, chills, and sleeping problems. Administration of synthetic and bioidentical forms of estrogen, such as estradiol valerate, has shown to improve these menopausal symptoms.

Type
Small Molecule
Groups
Approved, Investigational, Vet approved
Structure
Weight
Average: 356.4984
Monoisotopic: 356.23514489
Chemical Formula
C23H32O3
Synonyms
  • Estradiol valerate

Pharmacology

Indication

Estradiol valerate is commercially available as an intramuscular injection as the product Delestrogen and is indicated for the treatment of moderate to severe vasomotor symptoms and vulvovaginal atrophy due to menopause, for the treatment of hypoestrogenism due to hypogonadism, castration or primary ovarian failure, and for the treatment of advanced androgen-dependent carcinoma of the prostate (for palliation only).

Estradiol valerate is also available in combination with Dienogest as the commercially available product Natazia used for the prevention of pregnancy and for the treatment of heavy menstrual bleeding.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination to manageHeavy menstrual bleedingCombination Product in combination with: Dienogest (DB09123)••••••••••••
Used in combination for symptomatic treatment ofHypogonadismCombination Product in combination with: Norgestrel (DB09389)••••••••••••••••• •••• • ••••••••••••• •••• ••••••
Symptomatic treatment ofMenopausal symptoms••••••••••••
Used in combination for symptomatic treatment ofMenopauseCombination Product in combination with: Norgestrel (DB09389)••••••••••••••••• •••• • ••••••••••••• •••• ••••••
Used in combination to manageMenstrual irregularitiesCombination Product in combination with: Norgestrel (DB09389)••••••••••••••••••• ••••••
Associated Therapies
Contraindications & Blackbox Warnings
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Pharmacodynamics

Estrogen mediates its effects across the body through potent agonism of the Estrogen Receptor (ER), which is located in various tissues including in the breasts, uterus, ovaries, skin, prostate, bone, fat, and brain. Estradiol binds to both subtypes of the Estrogen Receptor: Estrogen Receptor Alpha (ERα) and Estrogen Receptor Beta (ERβ). Estradiol also acts as a potent agonist of G Protein-coupled Estrogen Receptor (GPER), which has recently been recognized as a major mediator of estradiol's rapid cellular effects 11.

Mechanism of action

Estradiol enters target cells freely (e.g., female organs, breasts, hypothalamus, pituitary) and interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary.

Increases in the down-stream effects of ER binding reverses some of the symptoms of menopause, which are primarily caused by a loss of estrogenic activity.

TargetActionsOrganism
AEstrogen receptor
agonist
Humans
AEstrogen receptor beta
agonist
Humans
UNuclear receptor subfamily 1 group I member 2Not AvailableHumans
UNeuronal acetylcholine receptor subunit alpha-4Not AvailableHumans
UNuclear receptor coactivator 2Not AvailableHumans
UG-protein coupled estrogen receptor 1Not AvailableHumans
UATP synthase subunit aNot AvailableHumans
UBeclin-1Not AvailableHumans
U17-beta-hydroxysteroid dehydrogenase type 2Not AvailableHumans
UEstrogen-related receptor gamma
ligand
Humans
Absorption

IM Injection: When conjugated with aryl and alkyl groups for parenteral administration, the rate of absorption of oily preparations is slowed with a prolonged duration of action, such that a single intramuscular injection of estradiol valerate or estradiol cypionate is absorbed over several weeks Label.

Natazia: After oral administration of estradiol valerate, cleavage to 17β-estradiol and valeric acid takes place during absorption by the intestinal mucosa or in the course of the first liver passage. This gives rise to estradiol and its metabolites, estrone and other metabolites. Maximum serum estradiol concentrations of 73.3 pg/mL are reached at a median of approximately 6 hours (range: 1.5–12 hours) and the area under the estradiol concentration curve [AUC(0–24h)] was 1301 pg·h/mL after single ingestion of a tablet containing 3 mg estradiol valerate under fasted condition on Day 1 of the 28-day sequential regimen.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Exogenous estrogens are metabolized using the same mechanism as endogenous estrogens. Estrogens are partially metabolized by cytochrome P450.

Hover over products below to view reaction partners

Route of elimination

Estradiol, estrone and estriol are excreted in the urine along with glucuronide and sulfate conjugates.

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
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
AbacavirAbacavir may decrease the excretion rate of Estradiol valerate which could result in a higher serum level.
AbametapirThe serum concentration of Estradiol valerate can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Estradiol valerate can be increased when combined with Abatacept.
AbciximabEstradiol valerate may decrease the anticoagulant activities of Abciximab.
AbemaciclibThe metabolism of Abemaciclib can be increased when combined with Estradiol valerate.
Food Interactions
  • Exercise caution with grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum concentration of estradiol valerate.
  • Exercise caution with St. John's Wort. This herb induces the CYP3A4 metabolism of estradiol valerate. Therefore it may reduce the serum concentration and effectiveness of estradiol valerate.

Products

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Active Moieties
NameKindUNIICASInChI Key
Estradiolprodrug4TI98Z838E50-28-2VOXZDWNPVJITMN-ZBRFXRBCSA-N
Product Images
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
DelestrogenInjection10 mg/1mLIntramuscularENDO USA, Inc.2007-11-01Not applicableUS flag
DelestrogenInjection10 mg/1mLIntramuscularMonarch Pharmaceuticals, Inc.1954-07-152007-10-01US flag
DelestrogenInjection40 mg/1mLIntramuscularENDO USA, Inc.2007-11-012024-09-30US flag
DelestrogenInjection40 mg/1mLIntramuscularMonarch Pharmaceuticals, Inc.1954-07-152007-10-01US flag
DelestrogenInjection20 mg/1mLIntramuscularENDO USA, Inc.2007-11-01Not applicableUS flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Estradiol ValerateInjection, solution20 mg/1mLIntramuscularPerrigo Company2010-03-31Not applicableUS flag
Estradiol ValerateInjection10 mg/1mLIntramuscularPar Pharmaceutical2012-06-012016-02-28US flag
Estradiol ValerateInjection20 mg/1mLIntramuscularHikma Pharmaceuticals USA Inc.2020-04-21Not applicableUS flag
Estradiol ValerateInjection10 mg/1mLIntramuscularSandoz S.P.A.2007-10-042010-01-31US flag
Estradiol valerateInjection10 mg/1mLIntramuscularXiromed, Llc2023-05-01Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
ARIORA 1MG/2MGEstradiol valerate (1 mg) + Dienogest (2 mg)TabletOral2017-01-01Not applicableGermany flag
ARIORA 1MG/2MGEstradiol valerate (1 mg) + Dienogest (2 mg)TabletOral2017-01-01Not applicableGermany flag
CLIMENEstradiol valerate (2 MG) + Estradiol valerate (2 mg) + Cyproterone acetate (1 mg)Kit; Tablet, coatedOralBayer Ag2014-07-08Not applicableItaly flag
CLIMENEstradiol valerate (2 MG) + Estradiol valerate (2 mg) + Cyproterone acetate (1 mg)Kit; Tablet, coatedOralBayer Ag2014-07-08Not applicableItaly flag
CLIMEN 28 SUGAR COATED TABLETEstradiol valerate (2 mg) + Estradiol valerate (2 mg) + Cyproterone acetate (1 mg)Kit; Tablet, coatedOralBAYER CO. (MALAYSIA) SDN. BHD.2020-09-082021-12-12Malaysia flag

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as steroid esters. These are compounds containing a steroid moiety which bears a carboxylic acid ester group.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Steroid esters
Direct Parent
Steroid esters
Alternative Parents
Estrogens and derivatives / 3-hydroxysteroids / Phenanthrenes and derivatives / Tetralins / 1-hydroxy-2-unsubstituted benzenoids / Carboxylic acid esters / Monocarboxylic acids and derivatives / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
1-hydroxy-2-unsubstituted benzenoid / 3-hydroxysteroid / Aromatic homopolycyclic compound / Benzenoid / Carbonyl group / Carboxylic acid derivative / Carboxylic acid ester / Estrane-skeleton / Estrogen-skeleton / Hydrocarbon derivative
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
steroid ester (CHEBI:31561) / C18 steroids (estrogens) and derivatives (C12859) / C18 steroids (estrogens) and derivatives (LMST02010039)
Affected organisms
Not Available

Chemical Identifiers

UNII
OKG364O896
CAS number
979-32-8
InChI Key
RSEPBGGWRJCQGY-RBRWEJTLSA-N
InChI
InChI=1S/C23H32O3/c1-3-4-5-22(25)26-21-11-10-20-19-8-6-15-14-16(24)7-9-17(15)18(19)12-13-23(20,21)2/h7,9,14,18-21,24H,3-6,8,10-13H2,1-2H3/t18-,19-,20+,21+,23+/m1/s1
IUPAC Name
(1S,3aS,3bR,9bS,11aS)-7-hydroxy-11a-methyl-1H,2H,3H,3aH,3bH,4H,5H,9bH,10H,11H,11aH-cyclopenta[a]phenanthren-1-yl pentanoate
SMILES
[H][C@@]12CC[C@H](OC(=O)CCCC)[C@@]1(C)CC[C@]1([H])C3=C(CC[C@@]21[H])C=C(O)C=C3

References

General References
  1. Pentikainen V, Erkkila K, Suomalainen L, Parvinen M, Dunkel L: Estradiol acts as a germ cell survival factor in the human testis in vitro. J Clin Endocrinol Metab. 2000 May;85(5):2057-67. [Article]
  2. Sharpe RM, Skakkebaek NE: Are oestrogens involved in falling sperm counts and disorders of the male reproductive tract? Lancet. 1993 May 29;341(8857):1392-5. [Article]
  3. Raman JD, Schlegel PN: Aromatase inhibitors for male infertility. J Urol. 2002 Feb;167(2 Pt 1):624-9. [Article]
  4. Carani C, Qin K, Simoni M, Faustini-Fustini M, Serpente S, Boyd J, Korach KS, Simpson ER: Effect of testosterone and estradiol in a man with aromatase deficiency. N Engl J Med. 1997 Jul 10;337(2):91-5. [Article]
  5. Behl C, Widmann M, Trapp T, Holsboer F: 17-beta estradiol protects neurons from oxidative stress-induced cell death in vitro. Biochem Biophys Res Commun. 1995 Nov 13;216(2):473-82. [Article]
  6. Schmidt JW, Wollner D, Curcio J, Riedlinger J, Kim LS: Hormone replacement therapy in menopausal women: Past problems and future possibilities. Gynecol Endocrinol. 2006 Oct;22(10):564-77. [Article]
  7. Foresta C, Zuccarello D, Biagioli A, De Toni L, Prana E, Nicoletti V, Ambrosini G, Ferlin A: Oestrogen stimulates endothelial progenitor cells via oestrogen receptor-alpha. Clin Endocrinol (Oxf). 2007 Oct;67(4):520-5. Epub 2007 Jun 15. [Article]
  8. Garcia-Segura LM, Sanz A, Mendez P: Cross-talk between IGF-I and estradiol in the brain: focus on neuroprotection. Neuroendocrinology. 2006;84(4):275-9. Epub 2006 Nov 23. [Article]
  9. O'Connell MB: Pharmacokinetic and pharmacologic variation between different estrogen products. J Clin Pharmacol. 1995 Sep;35(9S):18S-24S. doi: 10.1002/j.1552-4604.1995.tb04143.x. [Article]
  10. Dusterberg B, Nishino Y: Pharmacokinetic and pharmacological features of oestradiol valerate. Maturitas. 1982 Dec;4(4):315-24. [Article]
  11. Prossnitz ER, Barton M: Estrogen biology: new insights into GPER function and clinical opportunities. Mol Cell Endocrinol. 2014 May 25;389(1-2):71-83. doi: 10.1016/j.mce.2014.02.002. Epub 2014 Feb 12. [Article]
  12. W. KuhnzH. BlodeH. Zimmermann (1993). Pharmacokinetics of Exogenous Natural and Synthetic Estrogens and Antiestrogens. In: Estrogens and Antiestrogens II.. Springer, Berlin, Heidelberg. [ISBN:978-3-642-60107-1]
  13. FDA Thailand Product Information: Progynova (estradiol valerate) oral tablets [Link]
  14. FDA Approved Drug Products: Natazia (estradiol valerate and dienogest) tablets for oral use [Link]
KEGG Compound
C12859
PubChem Compound
13791
ChemSpider
13194
ChEBI
31561
ChEMBL
CHEMBL1511
ZINC
ZINC000003881556
RxList
RxList Drug Page
Wikipedia
Estradiol_valerate
FDA label
Download (317 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 RecruitingPreventionDrug Drug Interaction (DDI)1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableContraceptive1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableHypermenorrhea1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableInfertility / Polycystic Ovarian Syndrome (PCOS)1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableOral Contraceptives1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Kit; tablet, coatedOral
Tablet, coatedOral
Tablet
Tablet, sugar coatedOral
InjectionIntramuscular10 mg/1mL
InjectionIntramuscular20 mg/1mL
InjectionIntramuscular40 mg/1mL
LiquidIntramuscular10 mg / mL
TabletOral2 mg
Injection, solutionIntramuscular20 mg/1mL
Injection, solutionIntramuscular40 mg/1mL
Tablet, film coatedOral
Injection, solutionIntramuscular
TabletOral1 mg
Tablet, film coatedOral2 mg
SolutionIntramuscular; Parenteral
SolutionParenteral
KitOral
Kit; tablet, film coatedOral
SolutionIntramuscular
LiquidIntramuscular20 mg / mL
SolutionIntramuscular50 mg
TabletOral
TabletOral1.000 mg
TabletOral2.000 mg
Tablet, sugar coatedOral2 mg
InjectionParenteral10 mg
Tablet, sugar coatedOral
Tablet, coatedOral
Tablet, sugar coatedOral1 mg
Tablet, sugar coatedOral2 mg
TabletOral3.0000 mg
Tablet, film coatedOral1 mg
Tablet, coatedOral1 mg
Tablet, coatedOral2 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US6133251No2000-10-172016-10-25US flag
US8071577No2011-12-062026-05-13US flag
US8153616No2012-04-102028-01-30US flag
US6884793No2005-04-262016-10-25US flag

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000617 mg/mLALOGPS
logP5.28ALOGPS
logP5.78Chemaxon
logS-5.8ALOGPS
pKa (Strongest Acidic)10.33Chemaxon
pKa (Strongest Basic)-5.4Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count2Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area46.53 Å2Chemaxon
Rotatable Bond Count5Chemaxon
Refractivity102.89 m3·mol-1Chemaxon
Polarizability42.57 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-0059000000-f538dd75a4509c048c09
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-0019000000-8f3d14fa5b4145f57b38
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4r-0194000000-f6b89db344b2e5c09cc7
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-1069000000-90c0bf7d680bad68bc66
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-066r-9001000000-d343bfb29c71fec224b6
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-1000-3962000000-7a019421950f4281430d
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-196.4657659
predicted
DarkChem Lite v0.1.0
[M-H]-197.0777659
predicted
DarkChem Lite v0.1.0
[M-H]-189.5372
predicted
DeepCCS 1.0 (2019)
[M+H]+196.3607659
predicted
DarkChem Lite v0.1.0
[M+H]+197.5359659
predicted
DarkChem Lite v0.1.0
[M+H]+191.4326
predicted
DeepCCS 1.0 (2019)
[M+Na]+196.5987659
predicted
DarkChem Lite v0.1.0
[M+Na]+197.21065
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
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. Brama M, Gnessi L, Basciani S, Cerulli N, Politi L, Spera G, Mariani S, Cherubini S, Scotto d'Abusco A, Scandurra R, Migliaccio S: Cadmium induces mitogenic signaling in breast cancer cell by an ERalpha-dependent mechanism. Mol Cell Endocrinol. 2007 Jan 29;264(1-2):102-8. Epub 2006 Nov 27. [Article]
  2. Lehnes K, Winder AD, Alfonso C, Kasid N, Simoneaux M, Summe H, Morgan E, Iann MC, Duncan J, Eagan M, Tavaluc R, Evans CH Jr, Russell R, Wang A, Hu F, Stoica A: The effect of estradiol on in vivo tumorigenesis is modulated by the human epidermal growth factor receptor 2/phosphatidylinositol 3-kinase/Akt1 pathway. Endocrinology. 2007 Mar;148(3):1171-80. Epub 2006 Nov 30. [Article]
  3. Sasson S: Equilibrium binding analysis of estrogen agonists and antagonists: relation to the activation of the estrogen receptor. Pathol Biol (Paris). 1991 Jan;39(1):59-69. [Article]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
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. Vijayanathan V, Greenfield NJ, Thomas TJ, Ivanova MM, Tyulmenkov VV, Klinge CM, Gallo MA, Thomas T: Effects of estradiol and 4-hydroxytamoxifen on the conformation, thermal stability, and DNA recognition of estrogen receptor beta. Biochem Cell Biol. 2007 Feb;85(1):1-10. [Article]
  2. Sasson S: Equilibrium binding analysis of estrogen agonists and antagonists: relation to the activation of the estrogen receptor. Pathol Biol (Paris). 1991 Jan;39(1):59-69. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes
Specific Function
DNA-binding transcription activator activity, RNA polymerase II-specific
Gene Name
NR1I2
Uniprot ID
O75469
Uniprot Name
Nuclear receptor subfamily 1 group I member 2
Molecular Weight
49761.245 Da
References
  1. Xue Y, Moore LB, Orans J, Peng L, Bencharit S, Kliewer SA, Redinbo MR: Crystal structure of the pregnane X receptor-estradiol complex provides insights into endobiotic recognition. Mol Endocrinol. 2007 May;21(5):1028-38. Epub 2007 Feb 27. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane permeable to sodium ions
Specific Function
acetylcholine binding
Gene Name
CHRNA4
Uniprot ID
P43681
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-4
Molecular Weight
69956.47 Da
References
  1. Paradiso K, Zhang J, Steinbach JH: The C terminus of the human nicotinic alpha4beta2 receptor forms a binding site required for potentiation by an estrogenic steroid. J Neurosci. 2001 Sep 1;21(17):6561-8. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:23508108, PubMed:8670870, PubMed:9430642). Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1) (PubMed:23508108, PubMed:8670870, PubMed:9430642). Required with NCOA1 to control energy balance between white and brown adipose tissues (PubMed:23508108, PubMed:8670870, PubMed:9430642). Critical regulator of glucose metabolism regulation, acts as a RORA coactivator to specifically modulate G6PC1 expression (PubMed:23508108, PubMed:8670870, PubMed:9430642). Involved in the positive regulation of the transcriptional activity of the glucocorticoid receptor NR3C1 by sumoylation enhancer RWDD3 (PubMed:23508108). Positively regulates the circadian clock by acting as a transcriptional coactivator for the CLOCK-BMAL1 heterodimer (By similarity)
Specific Function
aryl hydrocarbon receptor binding
Gene Name
NCOA2
Uniprot ID
Q15596
Uniprot Name
Nuclear receptor coactivator 2
Molecular Weight
159155.645 Da
References
  1. Geistlinger TR, McReynolds AC, Guy RK: Ligand-selective inhibition of the interaction of steroid receptor coactivators and estrogen receptor isoforms. Chem Biol. 2004 Feb;11(2):273-81. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
G-protein coupled estrogen receptor that binds to 17-beta-estradiol (E2) with high affinity, leading to rapid and transient activation of numerous intracellular signaling pathways. Stimulates cAMP production, calcium mobilization and tyrosine kinase Src inducing the release of heparin-bound epidermal growth factor (HB-EGF) and subsequent transactivation of the epidermal growth factor receptor (EGFR), activating downstream signaling pathways such as PI3K/Akt and ERK/MAPK. Mediates pleiotropic functions among others in the cardiovascular, endocrine, reproductive, immune and central nervous systems. Has a role in cardioprotection by reducing cardiac hypertrophy and perivascular fibrosis in a RAMP3-dependent manner. Regulates arterial blood pressure by stimulating vasodilation and reducing vascular smooth muscle and microvascular endothelial cell proliferation. Plays a role in blood glucose homeostasis contributing to the insulin secretion response by pancreatic beta cells. Triggers mitochondrial apoptosis during pachytene spermatocyte differentiation. Stimulates uterine epithelial cell proliferation. Enhances uterine contractility in response to oxytocin. Contributes to thymic atrophy by inducing apoptosis. Attenuates TNF-mediated endothelial expression of leukocyte adhesion molecules. Promotes neuritogenesis in developing hippocampal neurons. Plays a role in acute neuroprotection against NMDA-induced excitotoxic neuronal death. Increases firing activity and intracellular calcium oscillations in luteinizing hormone-releasing hormone (LHRH) neurons. Inhibits early osteoblast proliferation at growth plate during skeletal development. Inhibits mature adipocyte differentiation and lipid accumulation. Involved in the recruitment of beta-arrestin 2 ARRB2 at the plasma membrane in epithelial cells. Functions also as a receptor for aldosterone mediating rapid regulation of vascular contractibility through the PI3K/ERK signaling pathway. Involved in cancer progression regulation. Stimulates cancer-associated fibroblast (CAF) proliferation by a rapid genomic response through the EGFR/ERK transduction pathway. Associated with EGFR, may act as a transcription factor activating growth regulatory genes (c-fos, cyclin D1). Promotes integrin alpha-5/beta-1 and fibronectin (FN) matrix assembly in breast cancer cells
Specific Function
chromatin binding
Gene Name
GPER1
Uniprot ID
Q99527
Uniprot Name
G-protein coupled estrogen receptor 1
Molecular Weight
42247.12 Da
References
  1. Thomas P, Dong J: Binding and activation of the seven-transmembrane estrogen receptor GPR30 by environmental estrogens: a potential novel mechanism of endocrine disruption. J Steroid Biochem Mol Biol. 2006 Dec;102(1-5):175-9. Epub 2006 Nov 7. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Key component of the proton channel; it may play a direct role in the translocation of protons across the membrane
Specific Function
proton transmembrane transporter activity
Gene Name
MT-ATP6
Uniprot ID
P00846
Uniprot Name
ATP synthase subunit a
Molecular Weight
24816.865 Da
References
  1. Van Dorst B, Mehta J, Rouah-Martin E, De Coen W, Blust R, Robbens J: The identification of cellular targets of 17beta estradiol using a lytic (T7) cDNA phage display approach. Toxicol In Vitro. 2011 Feb;25(1):388-93. doi: 10.1016/j.tiv.2010.10.012. Epub 2010 Oct 27. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Plays a central role in autophagy (PubMed:18570871, PubMed:21358617, PubMed:23184933, PubMed:23974797, PubMed:25484083, PubMed:28445460, PubMed:37776275). Acts as a core subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate; different complex forms are believed to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis. Involved in regulation of degradative endocytic trafficking and required for the abscission step in cytokinesis, probably in the context of PI3KC3-C2 (PubMed:20208530, PubMed:20643123, PubMed:23974797, PubMed:26783301). Essential for the formation of PI3KC3-C2 but not PI3KC3-C1 PI3K complex forms. Involved in endocytosis (PubMed:25275521). May play a role in antiviral host defense
Specific Function
GTPase binding
Gene Name
BECN1
Uniprot ID
Q14457
Uniprot Name
Beclin-1
Molecular Weight
51895.945 Da
References
  1. Van Dorst B, Mehta J, Rouah-Martin E, De Coen W, Blust R, Robbens J: The identification of cellular targets of 17beta estradiol using a lytic (T7) cDNA phage display approach. Toxicol In Vitro. 2011 Feb;25(1):388-93. doi: 10.1016/j.tiv.2010.10.012. Epub 2010 Oct 27. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Catalyzes the NAD-dependent oxidation of the highly active 17beta-hydroxysteroids, such as estradiol (E2), testosterone (T), and dihydrotestosterone (DHT), to their less active forms and thus regulates the biological potency of these steroids. Oxidizes estradiol to estrone, testosterone to androstenedione, and dihydrotestosterone to 5alpha-androstan-3,17-dione. Also has 20-alpha-HSD activity
Specific Function
17-alpha,20-alpha-dihydroxypregn-4-en-3-one dehydrogenase activity
Gene Name
HSD17B2
Uniprot ID
P37059
Uniprot Name
17-beta-hydroxysteroid dehydrogenase type 2
Molecular Weight
42784.75 Da
References
  1. Wetzel M, Marchais-Oberwinkler S, Perspicace E, Moller G, Adamski J, Hartmann RW: Introduction of an electron withdrawing group on the hydroxyphenylnaphthol scaffold improves the potency of 17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD2) inhibitors. J Med Chem. 2011 Nov 10;54(21):7547-57. doi: 10.1021/jm2008453. Epub 2011 Oct 19. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Ligand
General Function
Orphan receptor that acts as a transcription activator in the absence of bound ligand. Binds specifically to an estrogen response element and activates reporter genes controlled by estrogen response elements (By similarity). Induces the expression of PERM1 in the skeletal muscle
Specific Function
AF-2 domain binding
Gene Name
ESRRG
Uniprot ID
P62508
Uniprot Name
Estrogen-related receptor gamma
Molecular Weight
51305.485 Da
References
  1. Babu S, Vellore NA, Kasibotla AV, Dwayne HJ, Stubblefield MA, Uppu RM: Molecular docking of bisphenol A and its nitrated and chlorinated metabolites onto human estrogen-related receptor-gamma. Biochem Biophys Res Commun. 2012 Sep 21;426(2):215-20. doi: 10.1016/j.bbrc.2012.08.065. Epub 2012 Aug 23. [Article]

Enzymes

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, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). 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:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. 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). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
Specific Function
aromatase activity
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58406.915 Da
References
  1. Lee AJ, Cai MX, Thomas PE, Conney AH, Zhu BT: Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology. 2003 Aug;144(8):3382-98. [Article]
  2. Hong CC, Tang BK, Hammond GL, Tritchler D, Yaffe M, Boyd NF: Cytochrome P450 1A2 (CYP1A2) activity and risk factors for breast cancer: a cross-sectional study. Breast Cancer Res. 2004;6(4):R352-65. doi: 10.1186/bcr798. Epub 2004 May 7. [Article]
  3. Usmani KA, Cho TM, Rose RL, Hodgson E: Inhibition of the human liver microsomal and human cytochrome P450 1A2 and 3A4 metabolism of estradiol by deployment-related and other chemicals. Drug Metab Dispos. 2006 Sep;34(9):1606-14. doi: 10.1124/dmd.106.010439. Epub 2006 Jun 21. [Article]
  4. Chang SY, Chen C, Yang Z, Rodrigues AD: Further assessment of 17alpha-ethinyl estradiol as an inhibitor of different human cytochrome P450 forms in vitro. Drug Metab Dispos. 2009 Aug;37(8):1667-75. doi: 10.1124/dmd.109.026997. Epub 2009 May 19. [Article]
  5. CYP1A2 cancer.gov CTEP [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:15472229, PubMed:18004206, PubMed:18004212, PubMed:18719240, PubMed:19830808, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004206, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol, estrone and estriol (PubMed:15472229, PubMed:18719240, PubMed:23288867). Involved in the glucuronidation of bilirubin, a degradation product occurring in the normal catabolic pathway that breaks down heme in vertebrates (PubMed:17187418, PubMed:18004206, PubMed:19830808, PubMed:24525562). Also catalyzes the glucuronidation the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515). Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan (PubMed:12181437, PubMed:18004212, PubMed:20610558)
Specific Function
enzyme binding
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1A1
Molecular Weight
59590.91 Da
References
  1. Hanioka N, Tanabe N, Jinno H, Tanaka-Kagawa T, Nagaoka K, Naito S, Koeda A, Narimatsu S: Functional characterization of human and cynomolgus monkey UDP-glucuronosyltransferase 1A1 enzymes. Life Sci. 2010 Aug 14;87(7-8):261-8. doi: 10.1016/j.lfs.2010.07.001. Epub 2010 Jul 8. [Article]
  2. Guillemette C, Belanger A, Lepine J: Metabolic inactivation of estrogens in breast tissue by UDP-glucuronosyltransferase enzymes: an overview. Breast Cancer Res. 2004;6(6):246-54. Epub 2004 Sep 27. [Article]
  3. Kullak-Ublick GA, Ismair MG, Stieger B, Landmann L, Huber R, Pizzagalli F, Fattinger K, Meier PJ, Hagenbuch B: Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33. [Article]
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. Lee AJ, Cai MX, Thomas PE, Conney AH, Zhu BT: Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology. 2003 Aug;144(8):3382-98. [Article]
  2. Modugno F, Knoll C, Kanbour-Shakir A, Romkes M: A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human breast carcinogenesis. Breast Cancer Res Treat. 2003 Dec;82(3):191-7. doi: 10.1023/B:BREA.0000004376.21491.44. [Article]
  3. Flockhart Table of Drug Interactions [Link]
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. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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. Flockhart Table of Drug Interactions [Link]
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. Zhang Y, Gaikwad NW, Olson K, Zahid M, Cavalieri EL, Rogan EG: Cytochrome P450 isoforms catalyze formation of catechol estrogen quinones that react with DNA. Metabolism. 2007 Jul;56(7):887-94. doi: 10.1016/j.metabol.2007.03.001. [Article]
  2. Paracchini V, Pedotti P, Raimondi S, Garte S, Bradlow HL, Sepkovic DW, Taioli E: A common CYP1B1 polymorphism is associated with 2-OHE1/16-OHE1 urinary estrone ratio. Clin Chem Lab Med. 2005;43(7):702-6. doi: 10.1515/CCLM.2005.119. [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. Zhang Y, Gaikwad NW, Olson K, Zahid M, Cavalieri EL, Rogan EG: Cytochrome P450 isoforms catalyze formation of catechol estrogen quinones that react with DNA. Metabolism. 2007 Jul;56(7):887-94. doi: 10.1016/j.metabol.2007.03.001. [Article]
  2. Murray GI, Melvin WT, Greenlee WF, Burke MD: Regulation, function, and tissue-specific expression of cytochrome P450 CYP1B1. Annu Rev Pharmacol Toxicol. 2001;41:297-316. doi: 10.1146/annurev.pharmtox.41.1.297. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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. Cheng ZN, Shu Y, Liu ZQ, Wang LS, Ou-Yang DS, Zhou HH: Role of cytochrome P450 in estradiol metabolism in vitro. Acta Pharmacol Sin. 2001 Feb;22(2):148-54. [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:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). 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:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:15766564, PubMed:19965576, PubMed:7574697). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316)
Specific Function
arachidonic acid epoxygenase activity
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Kullak-Ublick GA, Ismair MG, Stieger B, Landmann L, Huber R, Pizzagalli F, Fattinger K, Meier PJ, Hagenbuch B: Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33. [Article]
  2. Cheng ZN, Shu Y, Liu ZQ, Wang LS, Ou-Yang DS, Zhou HH: Role of cytochrome P450 in estradiol metabolism in vitro. Acta Pharmacol Sin. 2001 Feb;22(2):148-54. [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 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. Modugno F, Knoll C, Kanbour-Shakir A, Romkes M: A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human breast carcinogenesis. Breast Cancer Res Treat. 2003 Dec;82(3):191-7. doi: 10.1023/B:BREA.0000004376.21491.44. [Article]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. Campusano M C, Brusco G F, Campino J C, Rodriguez P L, Arteaga U E: [Assessment of androgenic decline in the elderly]. Rev Med Chil. 2006 Sep;134(9):1123-8. Epub 2006 Dec 12. [Article]
  2. Kuba R, Pohanka M, Zakopcan J, Novotna I, Rektor I: Sexual dysfunctions and blood hormonal profile in men with focal epilepsy. Epilepsia. 2006 Dec;47(12):2135-40. [Article]
  3. Bendlova B, Zavadilova J, Vankova M, Vejrazkova D, Lukasova P, Vcelak J, Hill M, Cibula D, Vondra K, Starka L, Vrbikova J: Role of D327N sex hormone-binding globulin gene polymorphism in the pathogenesis of polycystic ovary syndrome. J Steroid Biochem Mol Biol. 2007 Apr;104(1-2):68-74. Epub 2007 Jan 26. [Article]
  4. Sablik Z, Samborska-Sablik A, Bolinska-Soltysiak H, Goch JH, Kula K: [Hyperandrogenism as a risk factor of coronary artery disease in young women]. Pol Arch Med Wewn. 2006 Feb;115(2):118-24. [Article]
  5. Mohamad MJ, Mohammad MA, Karayyem M, Hairi A, Hader AA: Serum levels of sex hormones in men with acute myocardial infarction. Neuro Endocrinol Lett. 2007 Apr;28(2):182-6. [Article]
  6. O'Connell MB: Pharmacokinetic and pharmacologic variation between different estrogen products. J Clin Pharmacol. 1995 Sep;35(9S):18S-24S. doi: 10.1002/j.1552-4604.1995.tb04143.x. [Article]
  7. Pardridge WM: Serum bioavailability of sex steroid hormones. Clin Endocrinol Metab. 1986 May;15(2):259-78. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
General Function
Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
Specific Function
antioxidant activity
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Albumin
Molecular Weight
69365.94 Da
References
  1. O'Connell MB: Pharmacokinetic and pharmacologic variation between different estrogen products. J Clin Pharmacol. 1995 Sep;35(9S):18S-24S. doi: 10.1002/j.1552-4604.1995.tb04143.x. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
General Function
FABPs are thought to play a role in the intracellular transport of long-chain fatty acids and their acyl-CoA esters. FABP2 is probably involved in triglyceride-rich lipoprotein synthesis. Binds saturated long-chain fatty acids with a high affinity, but binds with a lower affinity to unsaturated long-chain fatty acids. FABP2 may also help maintain energy homeostasis by functioning as a lipid sensor
Specific Function
fatty acid binding
Gene Name
FABP2
Uniprot ID
P12104
Uniprot Name
Fatty acid-binding protein, intestinal
Molecular Weight
15237.195 Da
References
  1. Rowland A, Knights KM, Mackenzie PI, Miners JO: Characterization of the binding of drugs to human intestinal fatty acid binding protein (IFABP): potential role of IFABP as an alternative to albumin for in vitro-in vivo extrapolation of drug kinetic parameters. Drug Metab Dispos. 2009 Jul;37(7):1395-403. doi: 10.1124/dmd.109.027656. Epub 2009 Apr 27. [Article]

Transporters

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. Romigi A, Vitrani G, Lo Giudice T, Centonze D, Franco V: Profile of pitolisant in the management of narcolepsy: design, development, and place in therapy. Drug Des Devel Ther. 2018 Aug 30;12:2665-2675. doi: 10.2147/DDDT.S101145. eCollection 2018. [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]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Mediates the Na(+)-independent transport of steroid sulfate conjugates and other specific organic anions (PubMed:10873595, PubMed:11159893, PubMed:11932330, PubMed:12724351, PubMed:14610227, PubMed:16908597, PubMed:18501590, PubMed:20507927, PubMed:22201122, PubMed:23531488, PubMed:25132355, PubMed:26383540, PubMed:27576593, PubMed:28408210, PubMed:29871943, PubMed:34628357). Responsible for the transport of estrone 3-sulfate (E1S) through the basal membrane of syncytiotrophoblast, highlighting a potential role in the placental absorption of fetal-derived sulfated steroids including the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S) (PubMed:11932330, PubMed:12409283). Also facilitates the uptake of sulfated steroids at the basal/sinusoidal membrane of hepatocytes, therefore accounting for the major part of organic anions clearance of liver (PubMed:11159893). Mediates the intestinal uptake of sulfated steroids (PubMed:12724351, PubMed:28408210). Mediates the uptake of the neurosteroids DHEA-S and pregnenolone sulfate (PregS) into the endothelial cells of the blood-brain barrier as the first step to enter the brain (PubMed:16908597, PubMed:25132355). Also plays a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons (PubMed:25132355). May act as a heme transporter that promotes cellular iron availability via heme oxygenase/HMOX2 and independently of TFRC (PubMed:35714613). Also transports heme by-product coproporphyrin III (CPIII), and may be involved in their hepatic disposition (PubMed:26383540). Mediates the uptake of other substrates such as prostaglandins D2 (PGD2), E1 (PGE1) and E2 (PGE2), taurocholate, L-thyroxine, leukotriene C4 and thromboxane B2 (PubMed:10873595, PubMed:14610227, PubMed:19129463, PubMed:29871943, Ref.25). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable). Shows a pH-sensitive substrate specificity 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:14610227, PubMed:19129463, PubMed:22201122). The exact transport mechanism has not been yet deciphered but most likely involves an anion exchange, coupling the cellular uptake of organic substrate with the efflux of an anionic compound (PubMed:19129463, PubMed:20507927, PubMed:26277985). Hydrogencarbonate/HCO3(-) acts as a probable counteranion that exchanges for organic anions (PubMed:19129463). Cytoplasmic glutamate may also act as counteranion in the placenta (PubMed:26277985). An inwardly directed proton gradient has also been proposed as the driving force of E1S uptake with a (H(+):E1S) stoichiometry of (1:1) (PubMed:20507927)
Specific Function
bile acid transmembrane transporter activity
Gene Name
SLCO2B1
Uniprot ID
O94956
Uniprot Name
Solute carrier organic anion transporter family member 2B1
Molecular Weight
76697.93 Da
References
  1. Tamai I, Nozawa T, Koshida M, Nezu J, Sai Y, Tsuji A: Functional characterization of human organic anion transporting polypeptide B (OATP-B) in comparison with liver-specific OATP-C. Pharm Res. 2001 Sep;18(9):1262-9. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Na(+)-independent transporter that mediates the cellular uptake of a broad range of organic anions such as the endogenous bile salts cholate and deoxycholate, either in their unconjugated or conjugated forms (taurocholate and glycocholate), at the plasmam membrane (PubMed:19129463, PubMed:7557095). Responsible for intestinal absorption of bile acids (By similarity). Transports dehydroepiandrosterone 3-sulfate (DHEAS), a major circulating steroid secreted by the adrenal cortex, as well as estrone 3-sulfate and 17beta-estradiol 17-O-(beta-D-glucuronate) (PubMed:11159893, PubMed:12568656, PubMed:19129463, PubMed:23918469, PubMed:25560245, PubMed:9539145). Mediates apical uptake of all-trans-retinol (atROL) across human retinal pigment epithelium, which is essential to maintaining the integrity of the visual cycle and thus vision (PubMed:25560245). Involved in the uptake of clinically used drugs (PubMed:17301733, PubMed:20686826, PubMed:27777271). Capable of thyroid hormone transport (both T3 or 3,3',5'-triiodo-L-thyronine, and T4 or L-tyroxine) (PubMed:19129463, PubMed:20358049). Also transports prostaglandin E2 (PubMed:19129463). Plays roles in blood-brain and -cerebrospinal fluid barrier transport of organic anions and signal mediators, and in hormone uptake by neural cells (By similarity). May also play a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons (PubMed:25132355). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel (PubMed:23243220). Shows a pH-sensitive substrate specificity 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). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
Specific Function
bile acid transmembrane transporter activity
Gene Name
SLCO1A2
Uniprot ID
P46721
Uniprot Name
Solute carrier organic anion transporter family member 1A2
Molecular Weight
74144.105 Da
References
  1. Kanai N, Lu R, Bao Y, Wolkoff AW, Vore M, Schuster VL: Estradiol 17 beta-D-glucuronide is a high-affinity substrate for oatp organic anion transporter. Am J Physiol. 1996 Feb;270(2 Pt 2):F326-31. [Article]
  2. Bossuyt X, Muller M, Hagenbuch B, Meier PJ: Polyspecific drug and steroid clearance by an organic anion transporter of mammalian liver. J Pharmacol Exp Ther. 1996 Mar;276(3):891-6. [Article]
  3. Kullak-Ublick GA, Ismair MG, Stieger B, Landmann L, Huber R, Pizzagalli F, Fattinger K, Meier PJ, Hagenbuch B: Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells. Lipophilic anion transporter that mediates ATP-dependent transport of glucuronide conjugates such as estradiol-17-beta-o-glucuronide and GSH conjugates such as leukotriene C4 (LTC4) (PubMed:12527806, PubMed:15256465). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Mediates multidrug resistance (MDR) in cancer cells by preventing the intracellular accumulation of certain antitumor drugs, such as, docetaxel and paclitaxel (PubMed:15256465, PubMed:23087055). Does not transport glycocholic acid, taurocholic acid, MTX, folic acid, cAMP, or cGMP (PubMed:12527806)
Specific Function
ABC-type glutathione S-conjugate transporter activity
Gene Name
ABCC10
Uniprot ID
Q5T3U5
Uniprot Name
ATP-binding cassette sub-family C member 10
Molecular Weight
161627.375 Da
References
  1. Chen ZS, Hopper-Borge E, Belinsky MG, Shchaveleva I, Kotova E, Kruh GD: Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10). Mol Pharmacol. 2003 Feb;63(2):351-8. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Antiporter that mediates the transport of conjugated steroids and other specific organic anions at the basal membrane of syncytiotrophoblast and at the apical membrane of proximal tubule epithelial cells, in exchange for anionic compounds (PubMed:10660625, PubMed:11907186, PubMed:15037815, PubMed:15102942, PubMed:15291761, PubMed:15576633, PubMed:17229912, PubMed:18501590, PubMed:26277985, PubMed:28027879). May be responsible for placental absorption of fetal-derived steroid sulfates such as estrone sulfate (E1S) and the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S), as well as clearing waste products and xenobiotics from the fetus (PubMed:12409283). Maybe also be involved in placental urate homeostasis (PubMed:17229912). Facilitates the renal reabsorption of organic anions such as urate and derived steroid sulfates (PubMed:15037815, PubMed:17229912). Organic anion glutarate acts as conteranion for E1S renal uptake (PubMed:15037815, PubMed:17229912). Possible transport mode may also include DHEA-S/E1S exchange (PubMed:28027879). Also interacts with inorganic anions such as chloride and hydroxyl ions, therefore possible transport modes may include E1S/Cl(-), E1S/OH(-), urate/Cl(-) and urate/OH(-) (PubMed:17229912). Also mediates the transport of prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may be involved in their renal excretion (PubMed:11907186). Also able to uptake anionic drugs, diuretics, bile salts and ochratoxin A (PubMed:10660625, PubMed:26277985). Mediates the unidirectional efflux of glutamate and aspartate (PubMed:28027879). Glutamate efflux down its transmembrane gradient may drive SLC22A11/OAT4-mediated placental uptake of E1S (PubMed:26277985)
Specific Function
organic anion transmembrane transporter activity
Gene Name
SLC22A11
Uniprot ID
Q9NSA0
Uniprot Name
Solute carrier family 22 member 11
Molecular Weight
59970.945 Da
References
  1. Cha SH, Sekine T, Kusuhara H, Yu E, Kim JY, Kim DK, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of multispecific organic anion transporter 4 expressed in the placenta. J Biol Chem. 2000 Feb 11;275(6):4507-12. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
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. Imai Y, Asada S, Tsukahara S, Ishikawa E, Tsuruo T, Sugimoto Y: Breast cancer resistance protein exports sulfated estrogens but not free estrogens. Mol Pharmacol. 2003 Sep;64(3):610-8. [Article]
  2. Imai Y, Tsukahara S, Ishikawa E, Tsuruo T, Sugimoto Y: Estrone and 17beta-estradiol reverse breast cancer resistance protein-mediated multidrug resistance. Jpn J Cancer Res. 2002 Mar;93(3):231-5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
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. Tamai I, Nozawa T, Koshida M, Nezu J, Sai Y, Tsuji A: Functional characterization of human organic anion transporting polypeptide B (OATP-B) in comparison with liver-specific OATP-C. Pharm Res. 2001 Sep;18(9):1262-9. [Article]
  2. Kullak-Ublick GA, Ismair MG, Stieger B, Landmann L, Huber R, Pizzagalli F, Fattinger K, Meier PJ, Hagenbuch B: Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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. Rao US, Fine RL, Scarborough GA: Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92. [Article]
  2. 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
General Function
Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient (PubMed:14586168, PubMed:15644426, PubMed:15846473, PubMed:16455804, PubMed:31553721). Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate) (PubMed:14586168, PubMed:15846473, PubMed:15864504, PubMed:22108572, PubMed:23832370). Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain (PubMed:11306713, PubMed:14586168, PubMed:15846473). E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange (PubMed:26377792). Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule (PubMed:11907186). Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate (PubMed:22108572, PubMed:23832370). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside (PubMed:15644426). May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate (PubMed:11669456, PubMed:15846473, PubMed:16455804). Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) (PubMed:14675047). May contribute to the release of cortisol in the adrenals (PubMed:15864504). Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile (By similarity). Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (By similarity). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB). In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity)
Specific Function
organic anion transmembrane transporter activity
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Organic anion transporter 3
Molecular Weight
59855.585 Da
References
  1. Cha SH, Sekine T, Fukushima JI, Kanai Y, Kobayashi Y, Goya T, Endou H: Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. Kullak-Ublick GA, Ismair MG, Stieger B, Landmann L, Huber R, Pizzagalli F, Fattinger K, Meier PJ, Hagenbuch B: Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Mediates the Na(+)-independent high affinity transport of organic anions such as the thyroid hormones L-thyroxine (T4), L-thyroxine sulfate (T4S), and 3,3',5'-triiodo-L-thyronine (reverse T3, rT3) at the plasma membrane (PubMed:12351693, PubMed:18566113, PubMed:19129463). Regulates T4 levels in different brain regions by transporting T4, and also by serving as an export pump for T4S, which is a source of T4 after hydrolysis by local sulfatases (PubMed:18566113). Increases the access of these substrates to the intracellular sites where they are metabolized by the deiodinases (PubMed:18566113). Other potential substrates, such as triiodothyronine (T3), 17-beta-glucuronosyl estradiol (17beta-estradiol 17-O-(beta-D-glucuronate)), estrone-3-sulfate (E1S) and sulfobromophthalein (BSP) are transported with much lower efficiency (PubMed:12351693, PubMed:19129463). Transports T4 and E1S in a pH-insensitive manner (PubMed:19129463). Facilitates the transport of thyroid hormones across the blood-brain barrier and into glia and neuronal cells in the brain (PubMed:30296914)
Specific Function
bile acid transmembrane transporter activity
Gene Name
SLCO1C1
Uniprot ID
Q9NYB5
Uniprot Name
Solute carrier organic anion transporter family member 1C1
Molecular Weight
78695.625 Da
References
  1. Pizzagalli F, Hagenbuch B, Stieger B, Klenk U, Folkers G, Meier PJ: Identification of a novel human organic anion transporting polypeptide as a high affinity thyroxine transporter. Mol Endocrinol. 2002 Oct;16(10):2283-96. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Organic anion antiporter with apparent broad substrate specificity. Recognizes various substrates including thyroid hormones 3,3',5-triiodo-L-thyronine (T3), L-thyroxine (T4) and 3,3',5'-triiodo-L-thyronine (rT3), conjugated steroids such as estrone 3-sulfate and estradiol 17-beta glucuronide, bile acids such as taurocholate and prostanoids such as prostaglandin E2, likely operating in a tissue-specific manner (PubMed:10873595, PubMed:19129463, PubMed:30343886). May be involved in uptake of metabolites from the circulation into organs such as kidney, liver or placenta. Possibly drives the selective transport of thyroid hormones and estrogens coupled to an outward glutamate gradient across the microvillous membrane of the placenta (PubMed:30343886). The transport mechanism, its electrogenicity and potential tissue-specific counterions remain to be elucidated (Probable)
Specific Function
organic anion transmembrane transporter activity
Gene Name
SLCO4A1
Uniprot ID
Q96BD0
Uniprot Name
Solute carrier organic anion transporter family member 4A1
Molecular Weight
77192.505 Da
References
  1. Tamai I, Nezu J, Uchino H, Sai Y, Oku A, Shimane M, Tsuji A: Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family. Biochem Biophys Res Commun. 2000 Jun 24;273(1):251-60. [Article]

Drug created at January 12, 2018 22:33 / Updated at November 03, 2024 19:35