Details of the Drug

General Information of Drug (ID: DM8SMD1)

Drug Name

Tazarotene

Synonyms

Avage; Suretin; Tazaroteno; Tazarotenum; Tazorac; Tazoral; Zorac; AGN 190168; AGN-190168; Avage (TN); Tazarotene [USAN:INN]; Tazorac (TN); Zorac (TN); Tazarotene (JAN/USAN/INN); Tazorac, Avage, Zora, Tazarotene; Ethyl 6-((4,4-dimethylthiochroman-6-yl)ethynyl)nicotinate; Ethyl 6-(2-(4,4-dimethylthiochroman-6-yl)ethynyl)nicotinate; Ethyl 6-[(4,4-dimethyl-3,4-dihydro-2H-thiochromen-6-yl)ethynyl]nicotinate; Ethyl 6-[2-(4,4-dimethyl-2,3-dihydrothiochromen-6-yl)ethynyl]pyridine-3-carboxylate; 3-Pyridinecarboxylic acid, 6-((3,4-dihydro-4,4-dimethyl-2H-1-benzothiopyran-6-yl)ethynyl)-, ethyl ester; 3-Pyridinecarboxylic acid, 6-((3,4-dihydro-4,4-dimethyl-2H-1-benzothiopyran-6-yl)ethynyl)-,ethyl ester

Indication

Disease Entry	ICD 11	Status	REF
Psoriasis vulgaris	EA90	Approved	[1], [2]

Therapeutic Class

Dermatologic Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

351.5

Topological Polar Surface Area (xlogp)

4.9

Rotatable Bond Count (rotbonds)

5

Hydrogen Bond Donor Count (hbonddonor)

0

Hydrogen Bond Acceptor Count (hbondacc)

4

ADMET Property

Clearance: The drug present in the plasma can be removed from the body at the rate of 37.2 mL/min/kg [3]
Half-life: The concentration or amount of drug in body reduced by one-half in 6.22 hours [3]
Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 3.55 L/kg [3]

Chemical Identifiers

Formula: C21H21NO2S
IUPAC Name: ethyl 6-[2-(4,4-dimethyl-2,3-dihydrothiochromen-6-yl)ethynyl]pyridine-3-carboxylate
Canonical SMILES: CCOC(=O)C1=CN=C(C=C1)C#CC2=CC3=C(C=C2)SCCC3(C)C
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
InChIKey: OGQICQVSFDPSEI-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 5381
ChEBI ID: CHEBI:32184
CAS Number: 118292-40-3
DrugBank ID: DB00799
TTD ID: D0BM5G
INTEDE ID: DR1536

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Retinoic acid receptor gamma (RARG)	TT1Q3IE	RARG_HUMAN	Binder	[4]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2C8 (CYP2C8)_{Main DME}	DES5XRU	CP2C8_HUMAN	Substrate	[5]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Psoriasis vulgaris

ICD Disease Classification

EA90

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Retinoic acid receptor gamma (RARG)	DTT	RARG	5.43E-04	-0.14	-0.37

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6952).
2	Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
3	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4	Recent developments in receptor-selective retinoids. Curr Pharm Des. 2000 Jun;6(9):919-31.
5	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.
6	Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
7	Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
8	Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
9	Differential expression and function of CYP2C isoforms in human intestine and liver. Pharmacogenetics. 2003 Sep;13(9):565-75.
10	Analysis of human cytochrome P450 2C8 substrate specificity using a substrate pharmacophore and site-directed mutants. Biochemistry. 2004 Dec 14;43(49):15379-92.
11	Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8.
12	PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9.
13	Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.
14	Targacept active conformation search: a new method for predicting the conformation of a ligand bound to its protein target. J Med Chem. 2004 Dec 30;47(27):6831-9.
15	Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):30-4.
16	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
17	Randomised controlled trial for emphysema with a selective agonist of the gamma-type retinoic acid receptor. Eur Respir J. 2012 Aug;40(2):306-12.
18	Therapeutic use of selective synthetic ligands for retinoic acid receptors: a patent review.Expert Opin Ther Pat. 2016 Aug;26(8):957-71.