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.drugbank.ca/drugs/DB00799https://www.ncbi.nlm.nih.gov/pubmed/26937021 | https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020600s008lbl.pdf
Curator's Comment: Description was created based on several sources, including https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020600s008lbl.pdf

Tazarotene a novel acetylenic retinoid is known to be effective in the topical treatment of psoriasis and acne. Tazarotene is rapidly and completely metabolized to its active metabolite tazarotenic acid. The exact mechanism of action of tazarotenic acid in the treatment of psoriasis and acne is not clearly defined. However, it is thought that the selective interaction of tazarotenic acid with the retinoic acid receptor (RAR) family (RARα, RARβ, and RARγ) and the subsequent induction of both positive and negative gene regulatory effects may be involved.

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 2678
Retinoic acid receptor alpha 11 Target ID: CHEMBL2055 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020600s008lbl.pdf	Agonist 2678
Retinoic acid receptor beta 18 Target ID: CHEMBL2008 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020600s008lbl.pdf	Agonist 2678
Retinoic acid receptor gamma 18 Target ID: CHEMBL2003 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020600s008lbl.pdf	Agonist 2678	40.0 nM [EC50]
Retinoic acid receptor beta 18 Target ID: CHEMBL2008 Sources: http://www.drugbank.ca/drugs/DB00799	Agonist 2678	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 2678	63.0 nM [EC50]

Conditions

Condition	Modality	Highest Phase	Product
Unknown 2578
Facial acne vulgaris 2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020600s008lbl.pdf	Primary	Approved 8429	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 2000
Plaque psoriasis 16 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020600s008lbl.pdf	Primary	Approved 8429	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 2000

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
The efficacy of 308nm laser treatment of psoriasis compared to historical controls.	2001 Dec	12165220
Practical management of psoriasis in the elderly: epidemiology, clinical aspects, quality of life, patient education and treatment options.	2002	12428994
Epithelial malignancies in organ transplant patients: clinical presentation and new methods of treatment.	2002	12079221
Treatment of cutaneous T cell lymphoma: current status and future directions.	2002	11978140
Successful treatment of acne vulgaris using a new method: results of a randomized vehicle-controlled trial of short-contact therapy with 0.1% tazarotene gel.	2002 Apr	11939810
Is TIG1 a new tumor suppressor in prostate cancer?	2002 Apr 3	11929940
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
Optimizing the use of tazarotene for the treatment of facial acne vulgaris through combination therapy.	2002 Feb	12095065
Once-daily tazarotene 0.1 % gel versus once-daily tretinoin 0.1 % microsponge gel for the treatment of facial acne vulgaris: a double-blind randomized trial.	2002 Feb	12095064
Tazarotene is an effective therapy for elastosis perforans serpiginosa.	2002 Feb	11843635
Treatment of warty dyskeratoma with tazarotenic acid.	2002 Feb	11807455
Refining retinoids with heteroatoms.	2002 Jun	12370069
Combination of calcipotriene (Dovonex) ointment and tazarotene (Tazorac) gel versus clobetasol ointment in the treatment of plaque psoriasis: a pilot study.	2002 Jun	12063489
Tazarotene (tazorac) for acne.	2002 Jun 10	12058150
Topical tazarotene therapy for psoriasis, acne vulgaris, and photoaging.	2002 Mar	12007011
A clinical evaluation of tazarotene 0.1% gel, with and without a high- or mid-high-potency corticosteroid, in patients with stable plaque psoriasis.	2002 Mar-Apr	11992180
Instrumental evaluation of retinoid-induced skin irritation.	2002 May	12060479
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
[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
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
Tazarotene 0.1% gel for psoriasis of the fingernails and toenails: an open, prospective study.	2003 Jul	12890227
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
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
A phase 1 study of tazarotene in adults with advanced cancer.	2003 Sep 1	12942109
Spotlight on adapalene in acne vulgaris.	2004	15554742
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
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
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
Current management strategies for cutaneous T-cell lymphoma.	2004 May-Jun	15262305
Phase II trial of the antiangiogenic agent IM862 in metastatic renal cell carcinoma.	2004 Nov 1	15354209
Topical tazarotene in acne vulgaris: treatment approaches.	2004 Oct	15543715
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
Comparison of topical retinoids in the treatment of acne.	2004 Sep-Oct	15556727

Patents

Sample Use Guides

In Vivo Use Guide

For psoriasis: It is recommended that treatment start with TAZORAC (Tazarotene) 0.05% Gel, with strength increased to 0.1% if tolerated and medically indicated. Apply TAZORAC® Gel once a day, in the evening, to psoriatic lesions, using enough (2 mg/cm2) to cover only the lesion with a thin film to no more than 20% of body surface area. If a bath or shower is taken prior to application, the skin should be dry before applying the gel. If emollients are used, they should be applied at least an hour before application of TAZORAC® Gel.

Route of Administration: Topical

In Vitro Use Guide

Tazarotene treatment caused a dose-dependent reduction in cell proliferation in BCC cell line ASZ001 cells (the strongest effect on cell proliferation was at 10 umol/L)

Substance Class	Chemical Created by `admin` on `Sat Dec 16 08:44:02 GMT 2023` Edited by `admin` on `Sat Dec 16 08:44:02 GMT 2023`
Record UNII	85FDJ14553
Record Status	`Validated (UNII)`
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Name

Type

Language

TAZAROTENIC ACID

Common Name

English

AGN-190299

Code

English

AGN190299

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