Tazarotene

Overview

Description
A medication used to treat fine wrinkles, uneven pigmentation spots on the skin, acne, and other skin reactions.
Description
A medication used to treat fine wrinkles, uneven pigmentation spots on the skin, acne, and other skin reactions.
DrugBank ID
DB00799
Type
Small Molecule
US Approved
YES
Other Approved
YES
Clinical Trials
Phase 0
2
Phase 1
16
Phase 2
19
Phase 3
20
Phase 4
16
Therapeutic Categories
  • Retinoids

Identification

Summary

Tazarotene is an acetylenic retinoid used to treat fine wrinkles, mottled pigmentation of the skin, acne vulgaris, and plaque psoriasis.

Brand Names
Arazlo, Duobrii, Fabior, Tazorac
Generic Name
Tazarotene
DrugBank Accession Number
DB00799
Background

Tazarotene, commonly marketed as Tazorac®, Avage®, and Zorac®, is member of the acetylenic class of retinoids. It is a prodrug that is found in topical formulations used in the treatment of various conditons, such as psoriasis, acne, and sun damaged skin (photodamage).

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 351.462
Monoisotopic: 351.129299611
Chemical Formula
C21H21NO2S
Synonyms
  • Tazarotene
  • Tazarotène
  • Tazaroteno
  • Tazarotenum
External IDs
  • AGN 190168
  • AGN-190168

Pharmacology

Indication

Used to treat psoriasis, acne and sun damaged skin (photodamage).

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofPlaque psoriasis••••••••••••
Symptomatic treatment ofBenign facial lentigines••••••••••••
Symptomatic treatment ofFacial fine wrinkling••••••••••••
Symptomatic treatment ofFacial hyperpigmentation••••••••••••
Symptomatic treatment ofFacial hypopigmentation••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Following topical application, tazarotene undergoes esterase hydrolysis to form its active metabolite, tazarotenic acid. When treating acne tazarotene may be taken in conjunction with an oral antibiotic. Tazarotene has been shown in peer-reviewed double blinded studies to reduce: mottling and hyperpigmentation, sallowness, fine wrinkling and coarse wrinkling in sun damaged skin. Histological studies have shown that long term (greater than 1 year) use of Tazarotene is associated with a significant reduction in atypical melanocytes and keratocytes - cells considered to be precursors of skin cancer. Some studies have shown long term use of Tazarotene to be associated with increased collagen production and better organization of skin collagen bundles.

Mechanism of action

Although the exact mechanism of tazarotene action is not known, studies have shown that the active form of the drug (tazarotenic acid) binds to all three members of the retinoic acid receptor (RAR) family: RARa, RARb, and RARg, but shows relative selectivity for RARb, and RARg and may modify gene expression. It also has affinity for RXR receptors.

TargetActionsOrganism
ARetinoic acid receptor alpha
agonist
Humans
ARetinoic acid receptor RXR-beta
agonist
Humans
ARetinoic acid receptor gamma
agonist
Humans
ARetinoic acid receptor beta
agonist
Humans
Absorption

Minimal systemic absorption of tazarotene occurs due to its rapid metabolism in the skin to the active metabolite, tazarotenic acid, which can be systemically absorbed and further metabolized. Gender had no influence on the systemic bioavailability of tazarotenic acid.

Volume of distribution

Not Available

Protein binding

The active form of the drug, tazarotenic acid, is highly bound to plasma proteins (>99%).

Metabolism

Undergoes esterase hydrolysis in skin to form its active metabolite, tazarotenic acid. Tazarotenic acid is further metabolized in skin and, after systemic absorption, hepatically metabolized to sulfoxides, sulfones, and other polar products for elimination.

Hover over products below to view reaction partners

Route of elimination

Tazarotene and tazarotenic acid were metabolized to sulfoxides, sulfones and other polar metabolites which were eliminated through urinary and fecal pathways.

Half-life

The half-life of the active form of the drug, tazarotenic acid, is approximately 18 hours in normal and psoriatic patients.

Clearance

Not Available

Adverse Effects
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Toxicity

Excessive topical use may lead to marked redness, peeling, or discomfort. Oral ingestion of the drug may affect liver function causing hypertriglyceridemia. Other symptoms may include conjunctival irritation, hair loss, headache, edema, fatigue, dermatitis, nausea, and visual disturbances. Oral administration of this material to rats and rabbits at doses of 0.20 mg/kg/day (rabbits) and 0.25 mg/kg/day (rats) resulted in developmental toxicity. A no effect level of 0.05 mg/kg/day was established. Similar teratogenic effects have been reported for other retinoid compounds.

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
AbataceptThe metabolism of Tazarotene can be increased when combined with Abatacept.
AbirateroneThe metabolism of Tazarotene can be decreased when combined with Abiraterone.
AdalimumabThe metabolism of Tazarotene can be increased when combined with Adalimumab.
AlmotriptanThe metabolism of Almotriptan can be decreased when combined with Tazarotene.
AlpelisibThe metabolism of Tazarotene can be decreased when combined with Alpelisib.
Food Interactions
No interactions found.

Products

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International/Other Brands
Zorac
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ArazloLotion0.045 % w/wTopicalBausch Health, Canada Inc.2021-09-16Not applicableCanada flag
ArazloLotion0.45 mg/1gTopicalBausch Health, Canada Inc.2019-12-19Not applicableUS flag
AvageCream1 mg/1gCutaneousAllergan, Inc.2003-01-072020-06-18US flag
FabiorAerosol, foam1 mg/1gTopicalStiefel Laboratories, Inc.2013-09-042018-09-30US flag
FabiorAerosol, foam1 mg/1gTopicalMayne Pharma Inc.2017-03-10Not applicableUS flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
TazaroteneCream1 mg/1gTopicalMayne Pharma Inc.2021-11-10Not applicableUS flag
TazaroteneCream0.5 mg/1gTopicalPacific Pharma, Inc.2017-04-152023-12-31US flag
TazaroteneCream1 mg/1gTopicalFougera Pharmaceuticals Inc.2019-01-28Not applicableUS flag
TazaroteneCream0.5 mg/1gTopicalPadagis Israel Pharmaceuticals Ltd2024-09-09Not applicableUS flag
TazaroteneGel0.5 mg/1gCutaneousSolaris Pharma Corporation2023-08-01Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
DuobriiTazarotene (0.045 % w/w) + Ulobetasol propionate (0.01 % w/w)LotionTopicalBausch Health, Canada Inc.2020-08-04Not applicableCanada flag
DuobriiTazarotene (0.45 mg/1g) + Ulobetasol propionate (0.1 mg/1g)LotionTopicalBausch Health, Canada Inc.2019-04-25Not applicableUS flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
011312 Niacinamide 4% / Tazarotene 0.05%Tazarotene (0.05 g/100g) + Nicotinamide (4 g/100g)CreamTopicalSincerus Florida, LLC2020-07-02Not applicableUS flag
Clindamycin 1% / Niacinamide 2% / Tazarotene 0.05%Tazarotene (0.05 g/100g) + Clindamycin phosphate (1 g/100g) + Nicotinamide (2 g/100g)GelTopicalSincerus Florida, LLC2019-05-10Not applicableUS flag
Hyaluronic Acid Sodium Salt 0.5% / Tazarotene 0.05%Tazarotene (0.05 g/100g) + Sodium hyaluronate (0.5 g/100g)CreamTopicalSincerus Florida, LLC2019-05-10Not applicableUS flag
Hyaluronic Acid Sodium Salt 0.5% / Tazarotene 0.1%Tazarotene (0.1 g/100g) + Sodium hyaluronate (0.5 g/100g)CreamTopicalSincerus Florida, LLC2019-05-07Not applicableUS flag
Niacinamide 4% / Tazarotene 0.05%Tazarotene (0.05 g/100g) + Nicotinamide (4 g/100g)CreamTopicalSincerus Florida, LLC2019-05-01Not applicableUS flag

Categories

ATC Codes
D05AX55 — Tazarotene and ulobetasolD05AX05 — Tazarotene
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as retinoids. These are oxygenated derivatives of 3,7-dimethyl-1-(2,6,6-trimethylcyclohex-1-enyl)nona-1,3,5,7-tetraene and derivatives thereof.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Prenol lipids
Sub Class
Retinoids
Direct Parent
Retinoids
Alternative Parents
Thiochromanes / Pyridinecarboxylic acids / 1-benzothiopyrans / Alkylarylthioethers / Thiopyrans / Benzenoids / Heteroaromatic compounds / Carboxylic acid esters / Monocarboxylic acids and derivatives / Azacyclic compounds
show 5 more
Substituents
1-benzothiopyran / Alkylarylthioether / Aromatic heteropolycyclic compound / Aryl thioether / Azacycle / Benzenoid / Benzothiopyran / Carboxylic acid derivative / Carboxylic acid ester / Heteroaromatic compound
show 16 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
ethyl ester, retinoid, pyridines, acetylenic compound, thiochromane (CHEBI:32184)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
81BDR9Y8PS
CAS number
118292-40-3
InChI Key
OGQICQVSFDPSEI-UHFFFAOYSA-N
InChI
InChI=1S/C21H21NO2S/c1-4-24-20(23)16-7-9-17(22-14-16)8-5-15-6-10-19-18(13-15)21(2,3)11-12-25-19/h6-7,9-10,13-14H,4,11-12H2,1-3H3
IUPAC Name
ethyl 6-[2-(4,4-dimethyl-3,4-dihydro-2H-1-benzothiopyran-6-yl)ethynyl]pyridine-3-carboxylate
SMILES
CCOC(=O)C1=CN=C(C=C1)C#CC1=CC2=C(SCCC2(C)C)C=C1

References

Synthesis Reference

Samuele Frigoli, Claudio Fuganti, Stefano Serra, Francesco Pizzocaro, Angelo Bedeschi, Paolo Tubertini, "Process for the preparation of Tazarotene." U.S. Patent US20060205950, issued September 14, 2006.

US20060205950
General References
  1. FDA Approved Drug Products: ARAZLO (tazarotene) lotion [Link]
  2. FDA Approved Drug Products: AVAGE (tazarotene) cream [Link]
  3. FDA Approved Drug Products: FABIOR (tazarotene) foam [Link]
  4. FDA Approved Drug Products: TAZORAC (tazarotene) gel [Link]
Human Metabolome Database
HMDB0014937
KEGG Drug
D01132
KEGG Compound
C12531
PubChem Compound
5381
PubChem Substance
46508992
ChemSpider
5188
BindingDB
50265951
RxNav
83947
ChEBI
32184
ChEMBL
CHEMBL1657
ZINC
ZINC000001542199
Therapeutic Targets Database
DAP000462
PharmGKB
PA164746821
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Tazarotene
FDA label
Download (90.3 KB)
MSDS
Download (25.7 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 AvailableCompletedTreatmentActinic Keratosis (AK)1somestatusstop reasonjust information to hide
Not AvailableCompletedTreatmentAtrophic Post Acne Scarring1somestatusstop reasonjust information to hide
Not AvailableCompletedTreatmentCancer / Hutchinson's Melanotic Freckle1somestatusstop reasonjust information to hide
Not AvailableCompletedTreatmentRetinoid Intolerance / Sun Damaged Skin1somestatusstop reasonjust information to hide
Not AvailableCompletedTreatmentScalp Psoriasis1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
  • Allergan inc
Packagers
  • Allergan Inc.
  • Physicians Total Care Inc.
Dosage Forms
FormRouteStrength
LotionTopical0.045 % w/w
LotionTopical0.45 mg/1g
LotionTopical
Aerosol, foamTopical1 mg/1g
CreamCutaneous1.000 mg
CreamTopical
GelTopical
GelCutaneous
CreamTopical0.5 mg/1g
CreamTopical1 mg/1g
GelTopical0.5 mg/1g
GelTopical1 mg/1g
GelTopical0.1 g
GelTopical0.05 g
CreamCutaneous0.05 mg/1g
CreamCutaneous0.1 mg/1g
CreamCutaneous0.5 mg/1g
CreamCutaneous1 mg/1g
CreamTopical0.05 %
CreamTopical0.1 %
GelCutaneous0.5 mg/1g
GelCutaneous1 mg/1g
GelOral1 mg/1g
GelTopical0.05 %
GelTopical0.1 %
GelCutaneous0.05 g/100g
GelCutaneous0.1 g/100g
GelTopical
Prices
Unit descriptionCostUnit
Tazorac 0.1% Gel 100 gm Tube638.75USD tube
Tazorac 0.05% Gel 100 gm Tube601.14USD tube
Tazorac 60 gm Tube .1% 60 gm Tube383.22USD tube
Tazorac 60 gm Tube .05% 60 gm Tube360.72USD tube
Tazorac 0.1% Gel 30 gm Tube191.64USD tube
Tazorac 30 gm Tube .1% 30 gm Tube191.64USD tube
Tazorac 0.05% Cream 30 gm Tube180.39USD tube
Tazorac 0.05% Gel 30 gm Tube180.39USD tube
Tazorac 0.1% cream5.59USD g
Tazorac 0.05% cream5.26USD g
Tazorac 0.05 % Gel1.49USD g
Tazorac 0.1 % Gel1.49USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5914334No1999-06-222014-06-07US flag
US5089509No1992-02-182011-06-13US flag
CA2191773No2004-08-102015-08-10Canada flag
US8808716No2014-08-192030-02-24US flag
US8809307No2014-08-192031-11-02US flag
US6517847No2003-02-112020-08-03US flag
US10251895No2019-04-092036-06-06US flag
US10478502No2019-11-192031-11-02US flag
US10426787No2019-10-012036-06-06US flag
US10568859No2020-02-252030-02-24US flag
US10688071No2020-06-232030-02-24US flag
US11311482No2018-05-112038-05-11US flag
US11679115No2016-06-062036-06-06US flag
US11648256No2016-06-062036-06-06US flag
US11679116No2016-06-062036-06-06US flag
US11839656No2011-11-022031-11-02US flag
US11986527No2011-11-022031-11-02US flag
US11957753No2011-11-022031-11-02US flag
US12076403No2011-11-022031-11-02US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilitySolubleNot Available
logP5.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00075 mg/mLALOGPS
logP5.15ALOGPS
logP5.22Chemaxon
logS-5.7ALOGPS
pKa (Strongest Basic)1.23Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count2Chemaxon
Hydrogen Donor Count0Chemaxon
Polar Surface Area39.19 Å2Chemaxon
Rotatable Bond Count5Chemaxon
Refractivity97.88 m3·mol-1Chemaxon
Polarizability40.31 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability1Chemaxon
Rule of FiveNoChemaxon
Ghose FilterYesChemaxon
Veber's RuleYesChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9936
Blood Brain Barrier+0.9675
Caco-2 permeable+0.5233
P-glycoprotein substrateSubstrate0.5758
P-glycoprotein inhibitor IInhibitor0.5422
P-glycoprotein inhibitor IINon-inhibitor0.5926
Renal organic cation transporterNon-inhibitor0.8219
CYP450 2C9 substrateNon-substrate0.7308
CYP450 2D6 substrateNon-substrate0.7687
CYP450 3A4 substrateSubstrate0.5187
CYP450 1A2 substrateInhibitor0.6172
CYP450 2C9 inhibitorInhibitor0.6385
CYP450 2D6 inhibitorNon-inhibitor0.8531
CYP450 2C19 inhibitorInhibitor0.6586
CYP450 3A4 inhibitorNon-inhibitor0.6387
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6124
Ames testNon AMES toxic0.8154
CarcinogenicityNon-carcinogens0.8925
BiodegradationNot ready biodegradable0.9946
Rat acute toxicity2.5435 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9968
hERG inhibition (predictor II)Non-inhibitor0.7757
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-004i-5059000000-5dfdf4638fc629294fd7
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-0udi-1590000000-a511655f5e07f3ab2179
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0uk9-0129000000-2db71aa7cf68c539db6d
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0udi-0009000000-f2e2860d56d550cf5c2d
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0udi-0009000000-e762236a34dfec49fbc3
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0udj-5019000000-41b6c2fe2b76a6635c27
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-0019000000-4ccbdbdd127423f1c85c
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-053r-0879000000-22086eb51ecfc39cb802
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-01t9-0191000000-ee019455e0a97e214631
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]-210.8176333
predicted
DarkChem Lite v0.1.0
[M-H]-210.6251333
predicted
DarkChem Lite v0.1.0
[M-H]-181.56845
predicted
DeepCCS 1.0 (2019)
[M+H]+212.4993333
predicted
DarkChem Lite v0.1.0
[M+H]+211.5877333
predicted
DarkChem Lite v0.1.0
[M+H]+183.92645
predicted
DeepCCS 1.0 (2019)
[M+Na]+211.0999333
predicted
DarkChem Lite v0.1.0
[M+Na]+211.2057333
predicted
DarkChem Lite v0.1.0
[M+Na]+190.98138
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Receptor for retinoic acid (PubMed:16417524, PubMed:19850744, PubMed:20215566, PubMed:21152046, PubMed:37478846). Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes (PubMed:28167758, PubMed:37478846, PubMed:21152046). The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (PubMed:19398580, PubMed:28167758). In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression (PubMed:16417524). On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation (PubMed:19850744, PubMed:20215566, PubMed:9267036, PubMed:37478846). Formation of a complex with histone deacetylases might lead to inhibition of RARE DNA element binding and to transcriptional repression (PubMed:28167758). Transcriptional activation and RARE DNA element binding might be supported by the transcription factor KLF2 (PubMed:28167758). RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis (By similarity). Has a role in the survival of early spermatocytes at the beginning prophase of meiosis (By similarity). In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes (By similarity). In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity). Together with RXRA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells (PubMed:28167758). In association with HDAC3, HDAC5 and HDAC7 corepressors, plays a role in the repression of microRNA-10a and thereby promotes the inflammatory response (PubMed:28167758)
Specific Function
alpha-actinin binding
Gene Name
RARA
Uniprot ID
P10276
Uniprot Name
Retinoic acid receptor alpha
Molecular Weight
50770.805 Da
References
  1. Baumann L, Vujevich J, Halem M, Martin LK, Kerdel F, Lazarus M, Pacheco H, Black L, Bryde J: Open-label pilot study of alitretinoin gel 0.1% in the treatment of photoaging. Cutis. 2005 Jul;76(1):69-73. [Article]
  2. Chandraratna RA: Tazarotene--first of a new generation of receptor-selective retinoids. Br J Dermatol. 1996 Oct;135 Suppl 49:18-25. [Article]
  3. Yen A, Fenning R, Chandraratna R, Walker P, Varvayanis S: A retinoic acid receptor beta/gamma-selective prodrug (tazarotene) plus a retinoid X receptor ligand induces extracellular signal-regulated kinase activation, retinoblastoma hypophosphorylation, G0 arrest, and cell differentiation. Mol Pharmacol. 2004 Dec;66(6):1727-37. Epub 2004 Sep 21. [Article]
  4. Meder W, Wendland M, Busmann A, Kutzleb C, Spodsberg N, John H, Richter R, Schleuder D, Meyer M, Forssmann WG: Characterization of human circulating TIG2 as a ligand for the orphan receptor ChemR23. FEBS Lett. 2003 Dec 18;555(3):495-9. [Article]
  5. Wang Q, Lee D, Sysounthone V, Chandraratna RAS, Christakos S, Korah R, Wieder R: 1,25-dihydroxyvitamin D3 and retonic acid analogues induce differentiation in breast cancer cells with function- and cell-specific additive effects. Breast Cancer Res Treat. 2001 May;67(2):157-68. [Article]
  6. Nagpal S, Chandraratna RA: Recent developments in receptor-selective retinoids. Curr Pharm Des. 2000 Jun;6(9):919-31. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE)
Specific Function
DNA-binding transcription activator activity, RNA polymerase II-specific
Gene Name
RXRB
Uniprot ID
P28702
Uniprot Name
Retinoic acid receptor RXR-beta
Molecular Weight
56921.38 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  3. Nagpal S, Chandraratna RA: Recent developments in receptor-selective retinoids. Curr Pharm Des. 2000 Jun;6(9):919-31. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. Required for limb bud development. In concert with RARA or RARB, required for skeletal growth, matrix homeostasis and growth plate function (By similarity)
Specific Function
chromatin binding
Gene Name
RARG
Uniprot ID
P13631
Uniprot Name
Retinoic acid receptor gamma
Molecular Weight
50341.405 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
  4. Arechalde A, Saurat JH: Management of psoriasis: the position of retinoid drugs. BioDrugs. 2000 May;13(5):327-33. [Article]
  5. 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
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence or presence of hormone ligand, acts mainly as an activator of gene expression due to weak binding to corepressors (PubMed:12554770). The RXRA/RARB heterodimer can act as a repressor on the DR1 element and as an activator on the DR5 element (PubMed:29021580). In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity)
Specific Function
DNA binding
Gene Name
RARB
Uniprot ID
P10826
Uniprot Name
Retinoic acid receptor beta
Molecular Weight
50488.63 Da
References
  1. Jones PH, Burnett RD, Fainaru I, Nadolny P, Walker P, Yu Z, Tang-Liu D, Ganesan TS, Talbot DC, Harris AL, Rustin GJ: A phase 1 study of tazarotene in adults with advanced cancer. Br J Cancer. 2003 Sep 1;89(5):808-15. [Article]
  2. Orlandi A, Bianchi L, Costanzo A, Campione E, Giusto Spagnoli L, Chimenti S: Evidence of increased apoptosis and reduced proliferation in basal cell carcinomas treated with tazarotene. J Invest Dermatol. 2004 Apr;122(4):1037-41. [Article]
  3. Chandraratna RA: Tazarotene--first of a new generation of receptor-selective retinoids. Br J Dermatol. 1996 Oct;135 Suppl 49:18-25. [Article]
  4. Arechalde A, Saurat JH: Management of psoriasis: the position of retinoid drugs. BioDrugs. 2000 May;13(5):327-33. [Article]
  5. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]

Enzymes

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. Attar M, Dong D, Ling KH, Tang-Liu DD: Cytochrome P450 2C8 and flavin-containing monooxygenases are involved in the metabolism of tazarotenic acid in humans. Drug Metab Dispos. 2003 Apr;31(4):476-81. doi: 10.1124/dmd.31.4.476. [Article]

Drug created at June 13, 2005 13:24 / Updated at November 09, 2024 05:58