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

General Information of Drug (ID: DM5ECDM)

• Drug Name: AGN-34 Drug Info
• Synonyms: AGN-34; CHEMBL190635; SCHEMBL1984049; 7-[2-(Hexyloxy)-3,5-diisopropylphenyl]-3-methyl-2,4,6-octatrienoic acid

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 9887925
  TTD Drug ID: DM5ECDM

Molecule-Related Drug Atlas

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Alitretinoin	DMME8LH	Kaposi sarcoma	2B57	Approved	[2]
Bexarotene	DMOBIKY	Cutaneous T-cell lymphoma	2B01	Approved	[3]
2-chloro-5-nitro-N-phenylbenzamide	DMUGQIV	Discovery agent	N.A.	Investigative	[4]
LG100754	DMEK4FY	Discovery agent	N.A.	Investigative	[5]
(5BETA)-PREGNANE-3,20-DIONE	DMVQ6RN	Discovery agent	N.A.	Investigative	[4]
Phytanic acid	DMSZ1RB	Discovery agent	N.A.	Investigative	[6]
CD3254	DM38MU1	Discovery agent	N.A.	Investigative	[7]
UVI3003	DM95UI1	Discovery agent	N.A.	Investigative	[8]
Tributylstannanyl	DMHN7CB	Discovery agent	N.A.	Investigative	[4]
methoprene acid	DM58A0W	Discovery agent	N.A.	Investigative	[9]

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	[10]
Alitretinoin	DMME8LH	Kaposi sarcoma	2B57	Approved	[2]
NRX-4204	DMYXOU2	Diabetic complication	5A2Y	Phase 2	[11]
IRX4204	DM9SCME	Breast cancer	2C60-2C65	Phase 1	[12]
9cUAB-30	DMYKPXJ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[13]
SR-11237	DMQG3CK	Solid tumour/cancer	2A00-2F9Z	Terminated	[14]
LG100754	DMEK4FY	Discovery agent	N.A.	Investigative	[15]

Drug(s) Targeting Farnesoid X-activated receptor (FXR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Chenodiol	DMQ8JIK	Cholelithiasis	DC11	Approved	[16]
Guggulsterone	DMP7LK1	Osteoarthritis	FA00-FA05	Approved	[17]
Obeticholic acid	DM3Q1SM	Primary biliary cholangitis	DB96.1	Approved	[18]
Bevacizumab + Trastuzumab	DM9CEI5	Breast cancer	2C60-2C65	Phase 3	[16]
GS-9674	DM936V7	Primary sclerosing cholangitis	DB96.2	Phase 3	[19]
Apomine	DM6B9HP	Osteopetrosis	LD24.10	Phase 2	[20]
LJN452	DM3XRUH	Primary biliary cholangitis	DB96.1	Phase 2	[21]
EYP001	DM5PBLM	Non-alcoholic steatohepatitis	DB92.1	Phase 2	[22]
EDP-305	DMGJYZ8	Non-alcoholic steatohepatitis	DB92.1	Phase 2	[23]
LMB763	DMQOXNL	Diabetic nephropathy	GB61.Z	Phase 2	[24]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Alitretinoin	DMME8LH	Kaposi sarcoma	2B57	Approved	[2]
LG100754	DMEK4FY	Discovery agent	N.A.	Investigative	[15]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Farnesoid X-activated receptor (FXR)	TTS4UGC	NR1H4_HUMAN	Inhibitor	[1]
Retinoic acid receptor RXR-alpha (RXRA)	TT6PEUO	RXRA_HUMAN	Inhibitor	[1]
Retinoic acid receptor RXR-beta (RXRB)	TTKLV96	RXRB_HUMAN	Inhibitor	[1]
Retinoic acid receptor RXR-gamma (RXRG)	TTH029C	RXRG_HUMAN	Inhibitor	[1]

References

• [1] Farnesoid X receptor: from structure to potential clinical applications. J Med Chem. 2005 Aug 25;48(17):5383-403.
• [2] 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.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [4] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [5] The rexinoid LG100754 is a novel RXR:PPARgamma agonist and decreases glucose levels in vivo. Mol Endocrinol. 2001 Aug;15(8):1360-9.
• [6] Phytanic acid is a retinoid X receptor ligand. Eur J Biochem. 1996 Feb 15;236(1):328-33.
• [7] Co-regulator recruitment and the mechanism of retinoic acid receptor synergy. Nature. 2002 Jan 10;415(6868):187-92.
• [8] 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.
• [9] 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.
• [10] Vitamins and cofactors: highlights of ESBOC 2009. Nat Chem Biol. 2009 Aug;5(8):530-3.
• [11] DOI: 10.1038/scibx.2010.766
• [12] Selective brain penetrable Nurr1 transactivator for treating Parkinson's disease.Oncotarget.2016 Feb 16;7(7):7469-79.
• [13] 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.
• [14] Silicon analogues of the RXR-selective retinoid agonist SR11237 (BMS649): chemistry and biology. ChemMedChem. 2009 Jul;4(7):1143-52.
• [15] Activation of specific RXR heterodimers by an antagonist of RXR homodimers. Nature. 1996 Oct 3;383(6599):450-3.
• [16] Lithocholic acid decreases expression of bile salt export pump through farnesoid X receptor antagonist activity. J Biol Chem. 2002 Aug 30;277(35):31441-7.
• [17] Effect of guggulsterone and cembranoids of Commiphora mukul on pancreatic phospholipase A(2): role in hypocholesterolemia. J Nat Prod. 2009 Jan;72(1):24-8.
• [18] 2016 FDA drug approvals. Nat Rev Drug Discov. 2017 Feb 2;16(2):73-76.
• [19] The Nonsteroidal Farnesoid X Receptor Agonist Cilofexor (GS-9674) Improves Markers of Cholestasis and Liver Injury in Patients With Primary Sclerosing Cholangitis. Hepatology. 2019 Sep;70(3):788-801.
• [20] The nuclear receptors FXR and LXRalpha: potential targets for the development of drugs affecting lipid metabolism and neoplastic diseases. Curr Pharm Des. 2001 Mar;7(4):231-59.
• [21] FXR modulators for enterohepatic and metabolic diseases.Expert Opin Ther Pat. 2018 Nov;28(11):765-782.
• [22] Clinical pipeline report, company report or official report of ENYO Pharma.
• [23] A novel non-bile acid FXR agonist EDP-305 potently suppresses liver injury and fibrosis without worsening of ductular reaction. Liver Int. 2020 Jul;40(7):1655-1669.
• [24] Nidufexor (LMB763), a Novel FXR Modulator for the Treatment of Nonalcoholic Steatohepatitis. J Med Chem. 2020 Apr 23;63(8):3868-3880.