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

General Information of Drug (ID: DMEK4FY)

• Drug Name: LG100754 Drug Info
• Synonyms: LG 100754; LG754

Indication

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

• Cross-matching ID:
  PubChem CID: 6442223
  CAS Number: CAS 180713-37-5
  TTD Drug ID: DMEK4FY

Molecule-Related Drug Atlas

Drug(s) Targeting PPAR-gamma messenger RNA (PPARG mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bardoxolone methyl	DMODA2X	Mixed connective tissue disease	4A43.3	Phase 3	[5]
AD-5075	DM1SLJ9	Type-2 diabetes	5A11	Terminated	[6]
2-chloro-5-nitro-N-phenylbenzamide	DMUGQIV	Discovery agent	N.A.	Investigative	[7]
L-783483	DM6OTGE	Discovery agent	N.A.	Investigative	[8]
L-796449	DMWTGQM	Discovery agent	N.A.	Investigative	[9]
L-165461	DMKBSGN	Discovery agent	N.A.	Investigative	[9]
AD-5061	DM5WV13	Discovery agent	N.A.	Investigative	[10]
TZD18	DMVCHOX	Discovery agent	N.A.	Investigative	[11]
(9Z,12E)-12-nitrooctadeca-9,12-dienoic acid	DM2REIN	Discovery agent	N.A.	Investigative	[12]
reglitazar	DMQ3ER0	Discovery agent	N.A.	Investigative	[13]

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	[14]
Bexarotene	DMOBIKY	Cutaneous T-cell lymphoma	2B01	Approved	[15]
2-chloro-5-nitro-N-phenylbenzamide	DMUGQIV	Discovery agent	N.A.	Investigative	[16]
AGN-34	DM5ECDM	Discovery agent	N.A.	Investigative	[17]
(5BETA)-PREGNANE-3,20-DIONE	DMVQ6RN	Discovery agent	N.A.	Investigative	[16]
Phytanic acid	DMSZ1RB	Discovery agent	N.A.	Investigative	[18]
CD3254	DM38MU1	Discovery agent	N.A.	Investigative	[19]
UVI3003	DM95UI1	Discovery agent	N.A.	Investigative	[20]
Tributylstannanyl	DMHN7CB	Discovery agent	N.A.	Investigative	[16]
methoprene acid	DM58A0W	Discovery agent	N.A.	Investigative	[21]

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	[22]
Alitretinoin	DMME8LH	Kaposi sarcoma	2B57	Approved	[14]
NRX-4204	DMYXOU2	Diabetic complication	5A2Y	Phase 2	[23]
IRX4204	DM9SCME	Breast cancer	2C60-2C65	Phase 1	[24]
9cUAB-30	DMYKPXJ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[25]
SR-11237	DMQG3CK	Solid tumour/cancer	2A00-2F9Z	Terminated	[26]
AGN-34	DM5ECDM	Discovery agent	N.A.	Investigative	[17]

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	[14]
AGN-34	DM5ECDM	Discovery agent	N.A.	Investigative	[17]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
PPAR-gamma messenger RNA (PPARG mRNA)	TTT2SVW	PPARG_HUMAN	Agonist	[2]
Retinoic acid receptor RXR-alpha (RXRA)	TT6PEUO	RXRA_HUMAN	Antagonist	[3]
Retinoic acid receptor RXR-beta (RXRB)	TTKLV96	RXRB_HUMAN	Antagonist	[4]
Retinoic acid receptor RXR-gamma (RXRG)	TTH029C	RXRG_HUMAN	Antagonist	[4]

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: 2814).
• [2] The antidiabetic agent LG100754 sensitizes cells to low concentrations of peroxisome proliferator-activated receptor gamma ligands. J Biol Chem. 2002 Apr 12;277(15):12503-6.
• [3] The rexinoid LG100754 is a novel RXR:PPARgamma agonist and decreases glucose levels in vivo. Mol Endocrinol. 2001 Aug;15(8):1360-9.
• [4] Activation of specific RXR heterodimers by an antagonist of RXR homodimers. Nature. 1996 Oct 3;383(6599):450-3.
• [5] A synthetic triterpenoid, 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO), is a ligand for the peroxisome proliferator-activated receptor gamma. Mol Endocrinol. 2000 Oct;14(10):1550-6.
• [6] Thiazolidinediones produce a conformational change in peroxisomal proliferator-activated receptor-gamma: binding and activation correlate with antidiabetic actions in db/db mice. Endocrinology. 1996 Oct;137(10):4189-95.
• [7] Tryptophan-containing dipeptide derivatives as potent PPARgamma antagonists: design, synthesis, biological evaluation, and molecular modeling. Eur J Med Chem. 2008 Dec;43(12):2699-716.
• [8] Novel peroxisome proliferator-activated receptor (PPAR) gamma and PPARdelta ligands produce distinct biological effects. J Biol Chem. 1999 Mar 5;274(10):6718-25.
• [9] Phenylacetic acid derivatives as hPPAR agonists. Bioorg Med Chem Lett. 2003 Apr 7;13(7):1277-80.
• [10] A novel oxyiminoalkanoic acid derivative, TAK-559, activates human peroxisome proliferator-activated receptor subtypes. Eur J Pharmacol. 2004 Jul 8;495(1):17-26.
• [11] A novel peroxisome proliferator-activated receptor alpha/gamma dual agonist demonstrates favorable effects on lipid homeostasis. Endocrinology. 2004 Apr;145(4):1640-8.
• [12] Activation of peroxisome proliferator-activated receptor gamma (PPARgamma) by nitroalkene fatty acids: importance of nitration position and degree ... J Med Chem. 2009 Aug 13;52(15):4631-9.
• [13] Pharmacological profiles of a novel oral antidiabetic agent, JTT-501, an isoxazolidinedione derivative. Eur J Pharmacol. 1999 Jan 8;364(2-3):211-9.
• [14] 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.
• [15] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [16] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [17] Farnesoid X receptor: from structure to potential clinical applications. J Med Chem. 2005 Aug 25;48(17):5383-403.
• [18] Phytanic acid is a retinoid X receptor ligand. Eur J Biochem. 1996 Feb 15;236(1):328-33.
• [19] Co-regulator recruitment and the mechanism of retinoic acid receptor synergy. Nature. 2002 Jan 10;415(6868):187-92.
• [20] 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.
• [21] 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.
• [22] Vitamins and cofactors: highlights of ESBOC 2009. Nat Chem Biol. 2009 Aug;5(8):530-3.
• [23] DOI: 10.1038/scibx.2010.766
• [24] Selective brain penetrable Nurr1 transactivator for treating Parkinson's disease.Oncotarget.2016 Feb 16;7(7):7469-79.
• [25] 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.
• [26] Silicon analogues of the RXR-selective retinoid agonist SR11237 (BMS649): chemistry and biology. ChemMedChem. 2009 Jul;4(7):1143-52.