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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 of TAZAROTENIC ACID

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
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.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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
Primary
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
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
5.44 pg/mL
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

AUC

ValueDoseCo-administeredAnalytePopulation
105.72 pg × h/mL
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

Doses

DosePopulationAdverse 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: 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: Page: p.812
DLT: Hypercalcaemia, Hypertriglyceridaemia...
Dose limiting toxicities:
Hypercalcaemia (grade 3, 17%)
Hypertriglyceridaemia (grade 4, 17%)
Sources: 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: 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: Page: p.812
DLT: Musculoskeletal pain...
Dose limiting toxicities:
Musculoskeletal pain (grade 3, 17%)
Sources: 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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Plaque psoriasis|Acne vulgaris
Sources: 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: Page: p.1
AEs

AEs

AESignificanceDosePopulation
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: 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: 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: 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: 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: 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: 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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Plaque psoriasis|Acne vulgaris
Sources: 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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Plaque psoriasis|Acne vulgaris
Sources: 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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Plaque psoriasis|Acne vulgaris
Sources: 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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Plaque psoriasis|Acne vulgaris
Sources: 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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Plaque psoriasis|Acne vulgaris
Sources: 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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Plaque psoriasis|Acne vulgaris
Sources: 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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Plaque psoriasis|Acne vulgaris
Sources: 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: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Plaque psoriasis|Acne vulgaris
Sources: Page: p.1
PubMed

PubMed

TitleDatePubMed
Management of scalp psoriasis: guidelines for corticosteroid use in combination treatment.
2001
The efficacy of 308nm laser treatment of psoriasis compared to historical controls.
2001 Dec
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
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
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
[Successful symptomatic tazarotene treatment of juvenile acanthosis nigricans of the familial obesity-associated type in insulin resistance].
2001 Jun
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
1,25-dihydroxyvitamin D3 and retonic acid analogues induce differentiation in breast cancer cells with function- and cell-specific additive effects.
2001 May
Treatment of psoriasis. Part 1. Topical therapy and phototherapy.
2001 Oct
The modern age of acne therapy: a review of current treatment options.
2001 Sep-Oct
Treatment of cutaneous T cell lymphoma: current status and future directions.
2002
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
Topical tazarotene therapy for psoriasis, acne vulgaris, and photoaging.
2002 Mar
Potential anti-inflammatory effects of topical retinoids and retinoid analogues.
2002 May-Jun
Drug interactions in psoriasis: the pros and cons of combining topical psoriasis therapies.
2002 May-Jun
Topical agents for the treatment of psoriasis, past, present and future.
2002 May-Jun
Treating keratosis pilaris.
2002 Sep
Retrospective analysis of the treatment of psoriasis of the palms and soles.
2003
Optimizing treatment with topical tazarotene.
2003
The rationale for using a topical retinoid for inflammatory acne.
2003
The efficacy of topical tazarotene monotherapy and combination therapies in psoriasis.
2003 Dec
Characterization of human circulating TIG2 as a ligand for the orphan receptor ChemR23.
2003 Dec 18
Acne cream can reverse sun damage.
2003 Feb
Management of acne.
2003 Jan
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
[Medication of the month. Tazarotene 0.05%-0.1% (Zorac)].
2003 Nov
Tazarotene-induced gene 3 is suppressed in basal cell carcinomas and reversed in vivo by tazarotene application.
2003 Oct
Tazarotene does not affect the pharmacokinetics and efficacy of a norethindrone/ethinylestradiol oral contraceptive.
2004
Tazarotene 0.1% gel for refractory mycosis fungoides lesions: an open-label pilot study.
2004 Apr
Oral tazarotene and oral pimecrolimus: novel oral therapies in development for psoriasis.
2004 Mar-Apr
Phase II trial of the antiangiogenic agent IM862 in metastatic renal cell carcinoma.
2004 Nov 1
Meta-analysis of topical tazarotene in the treatment of mild to moderate acne.
2004 Oct
Topical tazarotene: The BEST (balancing efficacy, speed, and tolerability) in acne trial.
2004 Oct
Topical retinoids in the management of acne: the best path to clear results.
2004 Oct
Patents

Sample Use Guides

In Vivo Use Guide
Unknown
Route of Administration: Unknown
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
  • 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
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