TAZAROTENIC ACID

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H17NO2S
Molecular Weight	323.409
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1(C)CCSC2=C1C=C(C=C2)C#CC3=CC=C(C=N3)C(O)=O

InChI

InChIKey=IQIBKLWBVJPOQO-UHFFFAOYSA-N

InChI=1S/C19H17NO2S/c1-19(2)9-10-23-17-8-4-13(11-16(17)19)3-6-15-7-5-14(12-20-15)18(21)22/h4-5,7-8,11-12H,9-10H2,1-2H3,(H,21,22)

HIDE SMILES / InChI

Molecular Formula	C19H17NO2S
Molecular Weight	323.409
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26937021 | https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020600s008lbl.pdfhttps://www.drugbank.ca/drugs/DB00799
Curator's Comment: Description was created based on several sources, including https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020600s008lbl.pdf

Tazarotene is a prodrug and a member of the acetylenic class of retinoids. 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. 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. Tazarotene is used to treat psoriasis, acne and sun damaged skin (photodamage). Tazarotene is marketed as Tazorac, Avage, Zorac, and Fabior.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Retinoic acid receptor gamma 18 Target ID: CHEMBL2003 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020600s008lbl.pdf	Agonist 2662
Retinoic acid receptor alpha 11 Target ID: CHEMBL2055 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020600s008lbl.pdf	Agonist 2662
Retinoic acid receptor beta 18 Target ID: CHEMBL2008 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020600s008lbl.pdf	Agonist 2662
Retinoic acid receptor gamma 18 Target ID: CHEMBL2003 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020600s008lbl.pdf	Agonist 2662	40.0 nM [EC50]
Retinoic acid receptor beta 18 Target ID: CHEMBL2008 Sources: http://www.drugbank.ca/drugs/DB00799	Agonist 2662	0.8 nM [EC50]
Retinoic acid receptor alpha 11 Target ID: CHEMBL2055 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020600s008lbl.pdf	Agonist 2662	63.0 nM [EC50]

Conditions

Condition	Modality	Highest Phase	Product
Unknown 2565
Facial acne vulgaris 2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020600s008lbl.pdf	Primary	Approved 8360	TAZORAC Approved Use TAZORAC® (tazarotene) Gel 0.05% and 0.1% are indicated for the topical treatment of patients with stable plaque psoriasis of up to 20% body surface area involvement. TAZORAC® (tazarotene) Gel 0.1% is also indicated for the topical treatment of patients with facial acne vulgaris of mild to moderate severity. Launch Date 9.700992E11
Plaque psoriasis 16 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020600s008lbl.pdf	Primary	Approved 8360	TAZORAC Approved Use TAZORAC® (tazarotene) Gel 0.05% and 0.1% are indicated for the topical treatment of patients with stable plaque psoriasis of up to 20% body surface area involvement. TAZORAC® (tazarotene) Gel 0.1% is also indicated for the topical treatment of patients with facial acne vulgaris of mild to moderate severity. Launch Date 9.700992E11

C_max

Value	Dose	Co-administered	Analyte	Population
5.44 pg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/31641413	5 mg single, topical dose: 5 mg route of administration: Topical experiment type: SINGLE co-administered:		TAZAROTENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
105.72 pg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/31641413	5 mg single, topical dose: 5 mg route of administration: Topical experiment type: SINGLE co-administered:		TAZAROTENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
33.6 mg 1 times / day multiple, oral Highest studied dose Dose: 33.6 mg, 1 times / day Route: oral Route: multiple Dose: 33.6 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12942109 Page: p.812	unhealthy, 39 – 72 n = 6 Health Status: unhealthy Condition: Advanced cancer Age Group: 39 – 72 Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/12942109 Page: p.812	DLT: Hypercalcaemia, Hypertriglyceridaemia... Dose limiting toxicities: Hypercalcaemia (grade 3, 17%) Hypertriglyceridaemia (grade 4, 17%) Sources: https://pubmed.ncbi.nlm.nih.gov/12942109 Page: p.812
25.2 mg 1 times / day multiple, oral MTD Dose: 25.2 mg, 1 times / day Route: oral Route: multiple Dose: 25.2 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12942109 Page: p.812	unhealthy, 39 – 72 n = 6 Health Status: unhealthy Condition: Advanced cancer Age Group: 39 – 72 Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/12942109 Page: p.812	DLT: Musculoskeletal pain... Dose limiting toxicities: Musculoskeletal pain (grade 3, 17%) Sources: https://pubmed.ncbi.nlm.nih.gov/12942109 Page: p.812
0.1 % 1 times / day multiple, topical Recommended Dose: 0.1 %, 1 times / day Route: topical Route: multiple Dose: 0.1 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020600s010lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Plaque psoriasis\|Acne vulgaris Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020600s010lbl.pdf Page: p.1	Disc. AE: Disorder fetal, Skin irritation... AEs leading to discontinuation/dose reduction: Disorder fetal Skin irritation Pruritus Burning skin Skin red Skin peeling Photosensitivity Sunburn Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020600s010lbl.pdf Page: p.1

AEs

AE	Significance	Dose	Population
Hypercalcaemia	grade 3, 17% DLT	33.6 mg 1 times / day multiple, oral Highest studied dose Dose: 33.6 mg, 1 times / day Route: oral Route: multiple Dose: 33.6 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12942109 Page: p.812	unhealthy, 39 – 72 n = 6 Health Status: unhealthy Condition: Advanced cancer Age Group: 39 – 72 Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/12942109 Page: p.812
Hypertriglyceridaemia	grade 4, 17% DLT	33.6 mg 1 times / day multiple, oral Highest studied dose Dose: 33.6 mg, 1 times / day Route: oral Route: multiple Dose: 33.6 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12942109 Page: p.812	unhealthy, 39 – 72 n = 6 Health Status: unhealthy Condition: Advanced cancer Age Group: 39 – 72 Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/12942109 Page: p.812
Musculoskeletal pain	grade 3, 17% DLT	25.2 mg 1 times / day multiple, oral MTD Dose: 25.2 mg, 1 times / day Route: oral Route: multiple Dose: 25.2 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12942109 Page: p.812	unhealthy, 39 – 72 n = 6 Health Status: unhealthy Condition: Advanced cancer Age Group: 39 – 72 Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/12942109 Page: p.812
Burning skin	Disc. AE	0.1 % 1 times / day multiple, topical Recommended Dose: 0.1 %, 1 times / day Route: topical Route: multiple Dose: 0.1 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020600s010lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Plaque psoriasis\|Acne vulgaris Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020600s010lbl.pdf Page: p.1
Disorder fetal	Disc. AE	0.1 % 1 times / day multiple, topical Recommended Dose: 0.1 %, 1 times / day Route: topical Route: multiple Dose: 0.1 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020600s010lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Plaque psoriasis\|Acne vulgaris Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020600s010lbl.pdf Page: p.1
Photosensitivity	Disc. AE	0.1 % 1 times / day multiple, topical Recommended Dose: 0.1 %, 1 times / day Route: topical Route: multiple Dose: 0.1 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020600s010lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Plaque psoriasis\|Acne vulgaris Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020600s010lbl.pdf Page: p.1
Pruritus	Disc. AE	0.1 % 1 times / day multiple, topical Recommended Dose: 0.1 %, 1 times / day Route: topical Route: multiple Dose: 0.1 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020600s010lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Plaque psoriasis\|Acne vulgaris Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020600s010lbl.pdf Page: p.1
Skin irritation	Disc. AE	0.1 % 1 times / day multiple, topical Recommended Dose: 0.1 %, 1 times / day Route: topical Route: multiple Dose: 0.1 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020600s010lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Plaque psoriasis\|Acne vulgaris Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020600s010lbl.pdf Page: p.1
Skin peeling	Disc. AE	0.1 % 1 times / day multiple, topical Recommended Dose: 0.1 %, 1 times / day Route: topical Route: multiple Dose: 0.1 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020600s010lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Plaque psoriasis\|Acne vulgaris Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020600s010lbl.pdf Page: p.1
Skin red	Disc. AE	0.1 % 1 times / day multiple, topical Recommended Dose: 0.1 %, 1 times / day Route: topical Route: multiple Dose: 0.1 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020600s010lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Plaque psoriasis\|Acne vulgaris Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020600s010lbl.pdf Page: p.1
Sunburn	Disc. AE	0.1 % 1 times / day multiple, topical Recommended Dose: 0.1 %, 1 times / day Route: topical Route: multiple Dose: 0.1 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020600s010lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Plaque psoriasis\|Acne vulgaris Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020600s010lbl.pdf Page: p.1

PubMed

Title	Date	PubMed
Tazarotene: the first receptor-selective topical retinoid for the treatment of psoriasis.	1997 Aug	9270551
Refining retinoids with heteroatoms.	2002 Jun	12370069
[Immunosuppresive agents, retinoids and new trends in the therapy of psoriasis].	2002 Nov	12501485
Oral lichen planus: a preliminary clinical study on treatment with tazarotene.	2002 Nov	12477060
Efficacy of 0.1% tazarotene cream for the treatment of photodamage: a 12-month multicenter, randomized trial.	2002 Nov	12437455
[Psoriatic onycho-pachydermo- periostitis].	2002 Oct	12399889
A comparison of psoralen plus ultraviolet A (PUVA) monotherapy, tacalcitol plus PUVA and tazarotene plus PUVA in patients with chronic plaque-type psoriasis.	2002 Oct	12366423
Retrospective analysis of the treatment of psoriasis of the palms and soles.	2003	14578095
Treatment of occupational koilonychia with tazarotene gel.	2003	12926806
Pharmacokinetics of tazarotene cream 0.1% after a single dose and after repeat topical applications at clinical or exaggerated application rates in patients with acne vulgaris or photodamaged skin.	2003	12885265
Optimizing treatment with topical tazarotene.	2003	12627995
The rationale for using a topical retinoid for inflammatory acne.	2003	12553848
Cytochrome P450 2C8 and flavin-containing monooxygenases are involved in the metabolism of tazarotenic acid in humans.	2003 Apr	12642475
Investigational therapies for psoriasis.	2003 Aug	12894137
Wrinkles.	2003 Dec	15555188
The efficacy of topical tazarotene monotherapy and combination therapies in psoriasis.	2003 Dec	14640932
Characterization of human circulating TIG2 as a ligand for the orphan receptor ChemR23.	2003 Dec 18	14675762
A systematic review of adverse effects associated with topical treatments for psoriasis.	2003 Feb	12639460
Acne cream can reverse sun damage.	2003 Feb	12632542
Cumulative irritation comparison of adapalene gel and solution with 2 tazarotene gels and 3 tretinoin formulations.	2003 Jul	12889719
Type I lamellar ichthyosis improved by tazarotene 0.1% gel.	2003 Jul	12823301
[Medication of the month. Tazarotene 0.05%-0.1% (Zorac)].	2003 Nov	14748200
Tazarotene-induced gene 3 is suppressed in basal cell carcinomas and reversed in vivo by tazarotene application.	2003 Oct	14632211
Comparison of prognostic factors in patients in phase I trials of cytotoxic drugs vs new noncytotoxic agents.	2003 Oct 6	14520440
Tazarotene does not affect the pharmacokinetics and efficacy of a norethindrone/ethinylestradiol oral contraceptive.	2004	15244497
Adapalene: a review of its use in the treatment of acne vulgaris.	2004	15212561
Tazarotene 0.1% cream for the treatment of photodamage.	2004 Apr	15146262
Evidence of increased apoptosis and reduced proliferation in basal cell carcinomas treated with tazarotene.	2004 Apr	15102095
Seborrheic keratoses: a study comparing the standard cryosurgery with topical calcipotriene, topical tazarotene, and topical imiquimod.	2004 Apr	15090020
Tazarotene 0.1% gel for refractory mycosis fungoides lesions: an open-label pilot study.	2004 Apr	15034511
The p73 gene is an anti-tumoral target of the RARbeta/gamma-selective retinoid tazarotene.	2004 Dec	15610529
Histological effects of tazarotene 0.1% cream vs. vehicle on photodamaged skin: a 6-month, multicentre, double-blind, randomized, vehicle-controlled study in patients with photodamaged facial skin.	2004 Dec	15606521
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.	2004 Dec	15383624
Treatment of lentigo maligna with tazarotene 0.1% gel.	2004 Jan	14699375
[Prescribe topical treatments for psoriasis].	2004 Jan 15	15049598
Topical treatment of basal cell carcinoma with tazarotene: a clinicopathological study on a large series of cases.	2004 Jul	15270884
Questions & answers. Of all the treatments that promise to improve the appearance of aging skin, which ones have been medically proven to actually work?	2004 Jul	15239171
Topical tazarotene chemoprevention reduces Basal cell carcinoma number and size in Ptch1+/- mice exposed to ultraviolet or ionizing radiation.	2004 Jul 1	15231643
Elephantiasis nostrum verrucosa of the abdomen: clinical results with tazarotene.	2004 Jul-Aug	15303792
Tazarotene 0.1% cream versus tretinoin 0.05% emollient cream in the treatment of photodamaged facial skin: a multicenter, double-blind, randomized, parallel-group study.	2004 Jun	15203997
Established treatments of psoriasis.	2004 Jun	15180467
Topical retinoid and antibiotic combination therapy for acne management.	2004 Mar-Apr	15098969
Oral tazarotene and oral pimecrolimus: novel oral therapies in development for psoriasis.	2004 Mar-Apr	15098968
Current management strategies for cutaneous T-cell lymphoma.	2004 May-Jun	15262305
Tazarotene: therapeutic strategies in the treatment of psoriasis, acne and photoaging.	2004 May-Jun	15087589
Phase II trial of the antiangiogenic agent IM862 in metastatic renal cell carcinoma.	2004 Nov 1	15354209
Topical retinoids in the management of acne: the best path to clear results.	2004 Oct	15543712
Retinoid therapy for psoriasis.	2004 Oct	15450342
Keratosis punctata palmoplantaris controlled with topical retinoids: a case report and review of the literature.	2004 Sep	15499759
Retinoid-mediated stimulation of steroid sulfatase activity in myeloid leukemic cell lines requires RARalpha and RXR and involves the phosphoinositide 3-kinase and ERK-MAP kinase pathways.	2006 Feb 1	16178010

Patents

Sample Use Guides

In Vivo Use Guide

Unknown

Route of Administration: Unknown

In Vitro Use Guide

In vitro enzyme kinetic parameters were determined for tazarotenic acid metabolite formation using 5 nM CYP26A1 or CYP26B1, 25 nM purified human reductase, and 0–10 μM tazarotenic acid. Incubations were carried out for 10 minutes at 37°C to ensure product linearity with regard to time and protein concentration. Additional experiments to determine the kinetic parameters for the sequential metabolism of tazarotenic acid metabolite sulfoxide used substrate concentrations ranging from 0 to 50 μM. Samples were prepared as described for in vitro metabolic profiling experiments.

Substance Class	Chemical Created by `admin` on `Thu Jul 06 14:11:42 UTC 2023` Edited by `admin` on `Thu Jul 06 14:11:42 UTC 2023`
Record UNII	85FDJ14553
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

TAZAROTENIC ACID

Common Name

English

AGN-190299

Code

English

AGN 190299

Code

English

3-PYRIDINECARBOXYLIC ACID, 6-(2-(3,4-DIHYDRO-4,4-DIMETHYL-2H-1-BENZOTHIOPYRAN-6-YL)ETHYNYL)-

Systematic Name

English

Code System Code Type Description

EPA CompTox

DTXSID60152094