Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMME8LH)

• Drug Name: Alitretinoin Drug Info

Indication

Disease Entry	ICD 11	Status	REF
Kaposi sarcoma	2B57	Approved	[1] , [2]

• Therapeutic Class: Anticancer Agents
• Cross-matching ID:
  PubChem CID: 449171
  ChEBI ID: CHEBI:50648
  CAS Number: CAS 5300-03-8
  TTD Drug ID: DMME8LH
  VARIDT Drug ID: DR00315
  INTEDE Drug ID: DR2501

Molecule-Related Drug Atlas

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Solid tumour/cancer	2A00-2F9Z	Approved	[7]
Progesterone	DMUY35B	Premature labour	JB00	Approved	[8]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[9]
Estradiol	DMUNTE3	Breast cancer	2C60-2C65	Approved	[10]
Acetaminophen	DMUIE76	Pain	MG30-MG3Z	Approved	[11]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[12]
Etoposide	DMNH3PG	Solid tumour/cancer	2A00-2F9Z	Approved	[13]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[14]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[8]
Verapamil	DMA7PEW	Hypertension	BA00-BA04	Approved	[15]

Drug(s) Targeting Retinoic acid receptor RXR-alpha (RXRA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bexarotene	DMOBIKY	Cutaneous T-cell lymphoma	2B01	Approved	[16]
2-chloro-5-nitro-N-phenylbenzamide	DMUGQIV	Discovery agent	N.A.	Investigative	[17]
AGN-34	DM5ECDM	Discovery agent	N.A.	Investigative	[18]
LG100754	DMEK4FY	Discovery agent	N.A.	Investigative	[19]
(5BETA)-PREGNANE-3,20-DIONE	DMVQ6RN	Discovery agent	N.A.	Investigative	[17]
Phytanic acid	DMSZ1RB	Discovery agent	N.A.	Investigative	[20]
CD3254	DM38MU1	Discovery agent	N.A.	Investigative	[21]
UVI3003	DM95UI1	Discovery agent	N.A.	Investigative	[22]
Tributylstannanyl	DMHN7CB	Discovery agent	N.A.	Investigative	[17]
methoprene acid	DM58A0W	Discovery agent	N.A.	Investigative	[23]

Drug(s) Targeting Retinoic acid receptor RXR-gamma (RXRG)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Vitamin A	DMJ2AH4	Night blindness	9D45	Approved	[24]
NRX-4204	DMYXOU2	Diabetic complication	5A2Y	Phase 2	[25]
IRX4204	DM9SCME	Breast cancer	2C60-2C65	Phase 1	[26]
9cUAB-30	DMYKPXJ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[27]
SR-11237	DMQG3CK	Solid tumour/cancer	2A00-2F9Z	Terminated	[28]
AGN-34	DM5ECDM	Discovery agent	N.A.	Investigative	[18]
LG100754	DMEK4FY	Discovery agent	N.A.	Investigative	[29]

Drug(s) Targeting Retinoic acid receptor RXR-beta (RXRB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AGN-34	DM5ECDM	Discovery agent	N.A.	Investigative	[18]
LG100754	DMEK4FY	Discovery agent	N.A.	Investigative	[29]

Drug(s) Targeting Retinoic acid receptor beta (RARB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tamibarotene	DM3G74J	T-cell leukaemia	2A90	Phase 3	[30]
PMID27336223-Compound-10	DMYUP6G	N. A.	N. A.	Patented	[31]
PMID27336223-Compound-8	DM460D1	N. A.	N. A.	Patented	[31]
PMID27336223-Compound-7	DM9QM6I	N. A.	N. A.	Patented	[31]
CD666	DMC8X9Y	Discovery agent	N.A.	Investigative	[32]
AGN193109	DMC0YOE	Discovery agent	N.A.	Investigative	[33]
AC55649	DM4JNY9	Discovery agent	N.A.	Investigative	[34]
BMS641	DMRT7G3	Discovery agent	N.A.	Investigative	[35]
AC261066	DMSKE1I	Discovery agent	N.A.	Investigative	[34]
TTNPB	DMSABD0	Discovery agent	N.A.	Investigative	[36]

Drug(s) Targeting Retinoic acid receptor gamma (RARG)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[4]
Trifarotene	DMOL793	Acne vulgaris	ED80	Approved	[37]
Tazarotene	DM8SMD1	Psoriasis vulgaris	EA90	Approved	[38]
Palovarotene	DMAD2OZ	Fibrodysplasia ossificans progressiva	FB31.1	Phase 3	[39]
PMID27336223-Compound-13	DMSZLYD	N. A.	N. A.	Patented	[31]
PMID27336223-Compound-12	DMT4P7K	N. A.	N. A.	Patented	[31]
PMID27336223-Compound-14	DMC41MA	N. A.	N. A.	Patented	[31]
PMID27336223-Compound-11	DMBN6KU	N. A.	N. A.	Patented	[31]
PMID27336223-Compound-15	DMIYCFE	N. A.	N. A.	Patented	[31]
PMID27336223-Compound-9	DM6V13W	N. A.	N. A.	Patented	[31]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Retinoic acid receptor beta (RARB)	TTISP28	RARB_HUMAN	Agonist	[3]
Retinoic acid receptor gamma (RARG)	TT1Q3IE	RARG_HUMAN	Modulator	[3] , [4] , [5]
Retinoic acid receptor RXR-alpha (RXRA)	TT6PEUO	RXRA_HUMAN	Agonist	[3]
Retinoic acid receptor RXR-beta (RXRB)	TTKLV96	RXRB_HUMAN	Agonist	[3]
Retinoic acid receptor RXR-gamma (RXRG)	TTH029C	RXRG_HUMAN	Agonist	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[6]

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: 2645).
• [2] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [3] 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.
• [4] 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.
• [5] Alitretinoin: a comprehensive review. Expert Opin Investig Drugs. 2008 Mar;17(3):437-43.
• [6] Alitretinoin in dermatology-an update. Indian J Dermatol. 2015 Sep-Oct;60(5):520.
• [7] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [8] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [9] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [10] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [11] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [12] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [13] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [14] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [15] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [16] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [17] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [18] Farnesoid X receptor: from structure to potential clinical applications. J Med Chem. 2005 Aug 25;48(17):5383-403.
• [19] The rexinoid LG100754 is a novel RXR:PPARgamma agonist and decreases glucose levels in vivo. Mol Endocrinol. 2001 Aug;15(8):1360-9.
• [20] Phytanic acid is a retinoid X receptor ligand. Eur J Biochem. 1996 Feb 15;236(1):328-33.
• [21] Co-regulator recruitment and the mechanism of retinoic acid receptor synergy. Nature. 2002 Jan 10;415(6868):187-92.
• [22] Characterization of the interaction between retinoic acid receptor/retinoid X receptor (RAR/RXR) heterodimers and transcriptional coactivators thro... J Biol Chem. 2005 Jan 14;280(2):1625-33.
• [23] Activation of mammalian retinoid X receptors by the insect growth regulator methoprene. Proc Natl Acad Sci U S A. 1995 Jun 20;92(13):6157-60.
• [24] Vitamins and cofactors: highlights of ESBOC 2009. Nat Chem Biol. 2009 Aug;5(8):530-3.
• [25] DOI: 10.1038/scibx.2010.766
• [26] Selective brain penetrable Nurr1 transactivator for treating Parkinson's disease.Oncotarget.2016 Feb 16;7(7):7469-79.
• [27] In vitro metabolic characterization, phenotyping, and kinetic studies of 9cUAB30, a retinoid X receptor-specific retinoid. Drug Metab Dispos. 2007 Jul;35(7):1157-64.
• [28] Silicon analogues of the RXR-selective retinoid agonist SR11237 (BMS649): chemistry and biology. ChemMedChem. 2009 Jul;4(7):1143-52.
• [29] Activation of specific RXR heterodimers by an antagonist of RXR homodimers. Nature. 1996 Oct 3;383(6599):450-3.
• [30] Tamibarotene: a candidate retinoid drug for Alzheimer's disease. Biol Pharm Bull. 2012;35(8):1206-12.
• [31] Therapeutic use of selective synthetic ligands for retinoic acid receptors: a patent review.Expert Opin Ther Pat. 2016 Aug;26(8):957-71.
• [32] Identification of synthetic retinoids with selectivity for human nuclear retinoic acid receptor gamma. Biochem Biophys Res Commun. 1992 Jul 31;186(2):977-83.
• [33] Therapeutic applications for ligands of retinoid receptors. Curr Pharm Des. 2000 Jan;6(1):25-58.
• [34] Discovery of a potent, orally available, and isoform-selective retinoic acid beta2 receptor agonist. J Med Chem. 2005 Dec 1;48(24):7517-9.
• [35] Rational design of RAR-selective ligands revealed by RARbeta crystal stucture. EMBO Rep. 2004 Sep;5(9):877-82.
• [36] 9-cis-retinoic acid analogues with bulky hydrophobic rings: new RXR-selective agonists. Bioorg Med Chem Lett. 2004 Dec 20;14(24):6117-22.
• [37] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [38] Recent developments in receptor-selective retinoids. Curr Pharm Des. 2000 Jun;6(9):919-31.
• [39] 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.