TAZAROTENIC ACID

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H17NO2S
Molecular Weight	323.4106
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1(C)CCSc2ccc(C#Cc3ccc(cn3)C(=O)O)cc21

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	323.4106
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 17 Target ID: CHEMBL2003 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020600s008lbl.pdf	Agonist 2458
Retinoic acid receptor alpha 11 Target ID: CHEMBL2055 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020600s008lbl.pdf	Agonist 2458
Retinoic acid receptor beta 17 Target ID: CHEMBL2008 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020600s008lbl.pdf	Agonist 2458
Retinoic acid receptor gamma 17 Target ID: CHEMBL2003 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020600s008lbl.pdf	Agonist 2458	40.0 nM [EC50]
Retinoic acid receptor beta 17 Target ID: CHEMBL2008 Sources: http://www.drugbank.ca/drugs/DB00799	Agonist 2458	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 2458	63.0 nM [EC50]

Conditions

Condition	Modality	Highest Phase	Product
Unknown 2501
Facial acne vulgaris 2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020600s008lbl.pdf	Primary	Approved 8003	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 15 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020600s008lbl.pdf	Primary	Approved 8003	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
Management of scalp psoriasis: guidelines for corticosteroid use in combination treatment.	2001	11577796
The efficacy of 308nm laser treatment of psoriasis compared to historical controls.	2001 Dec	12165220
Tazarotene cream for the treatment of facial photodamage: a multicenter, investigator-masked, randomized, vehicle-controlled, parallel comparison of 0.01%, 0.025%, 0.05%, and 0.1% tazarotene creams with 0.05% tretinoin emollient cream applied once daily for 24 weeks.	2001 Dec	11735710
Efficacy and tolerability of once-daily tazarotene 0.1% gel versus once-daily tretinoin 0.025% gel in the treatment of facial acne vulgaris: a randomized trial.	2001 Jun	11499329
Comparison of treatment of acne vulgaris with alternate-day applications of tazarotene 0.1% gel and once-daily applications of adapalene 0.1% gel: a randomized trial.	2001 Jun	11499327
[Successful symptomatic tazarotene treatment of juvenile acanthosis nigricans of the familial obesity-associated type in insulin resistance].	2001 Jun	11428078
Investigator-masked comparison of tazarotene gel q.d. plus mometasone furoate cream q.d. vs. mometasone furoate cream b.i.d. in the treatment of plaque psoriasis.	2001 Mar	11422529
1,25-dihydroxyvitamin D3 and retonic acid analogues induce differentiation in breast cancer cells with function- and cell-specific additive effects.	2001 May	11519864
Treatment of psoriasis. Part 1. Topical therapy and phototherapy.	2001 Oct	11568737
The modern age of acne therapy: a review of current treatment options.	2001 Sep-Oct	11514915
Treatment of cutaneous T cell lymphoma: current status and future directions.	2002	11978140
A multicenter, double-blind, randomized comparison study of the efficacy and tolerability of once-daily tazarotene 0.1% gel and adapalene 0.1% gel for the treatment of facial acne vulgaris.	2002 Feb	12095066
Topical tazarotene therapy for psoriasis, acne vulgaris, and photoaging.	2002 Mar	12007011
Potential anti-inflammatory effects of topical retinoids and retinoid analogues.	2002 May-Jun	12201351
Drug interactions in psoriasis: the pros and cons of combining topical psoriasis therapies.	2002 May-Jun	11976987
Topical agents for the treatment of psoriasis, past, present and future.	2002 May-Jun	11976984
Treating keratosis pilaris.	2002 Sep	12196765
Retrospective analysis of the treatment of psoriasis of the palms and soles.	2003	14578095
Optimizing treatment with topical tazarotene.	2003	12627995
The rationale for using a topical retinoid for inflammatory acne.	2003	12553848
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
Acne cream can reverse sun damage.	2003 Feb	12632542
Management of acne.	2003 Jan	12540312
Tazarotene cream in the treatment of psoriasis: Two multicenter, double-blind, randomized, vehicle-controlled studies of the safety and efficacy of tazarotene creams 0.05% and 0.1% applied once daily for 12 weeks.	2003 May	12734506
[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
Tazarotene does not affect the pharmacokinetics and efficacy of a norethindrone/ethinylestradiol oral contraceptive.	2004	15244497
Tazarotene 0.1% gel for refractory mycosis fungoides lesions: an open-label pilot study.	2004 Apr	15034511
Oral tazarotene and oral pimecrolimus: novel oral therapies in development for psoriasis.	2004 Mar-Apr	15098968
Phase II trial of the antiangiogenic agent IM862 in metastatic renal cell carcinoma.	2004 Nov 1	15354209
Meta-analysis of topical tazarotene in the treatment of mild to moderate acne.	2004 Oct	15543714
Topical tazarotene: The BEST (balancing efficacy, speed, and tolerability) in acne trial.	2004 Oct	15543713
Topical retinoids in the management of acne: the best path to clear results.	2004 Oct	15543712

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 `Sat Jun 26 10:57:34 UTC 2021` Edited by `admin` on `Sat Jun 26 10:57:34 UTC 2021`
Record UNII	85FDJ14553
Record Status	`Validated (UNII)`
Record Version

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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

118292-41-4

Created by admin on Sat Jun 26 10:57:34 UTC 2021 , Edited by admin on Sat Jun 26 10:57:34 UTC 2021

PRIMARY

CAS

118292-41-4

Created by admin on Sat Jun 26 10:57:34 UTC 2021 , Edited by admin on Sat Jun 26 10:57:34 UTC 2021

PRIMARY

FDA UNII

85FDJ14553

Created by admin on Sat Jun 26 10:57:34 UTC 2021 , Edited by admin on Sat Jun 26 10:57:34 UTC 2021

PRIMARY

PUBCHEM

147525

Created by admin on Sat Jun 26 10:57:34 UTC 2021 , Edited by admin on Sat Jun 26 10:57:34 UTC 2021

PRIMARY

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ACTIVE MOIETY

Name	Property Type	Amount	Referenced Substance	Defining	Parameters	References
Tmax	PHARMACOKINETIC

Details

SMILES

InChI

Originator

Approval Year

Targets

Conditions

Approved Use

Launch Date

Approved Use

Launch Date

Cmax

AUC

Doses

AEs

PubMed

Patents

Sample Use Guides

C_max