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

General Information of Drug (ID: DM6OTGE)

• Drug Name: L-783483 Drug Info
• Synonyms: F3MethylAA

Indication

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

• Cross-matching ID:
  PubChem CID: 9935197
  TTD Drug ID: DM6OTGE

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	[4]
AD-5075	DM1SLJ9	Type-2 diabetes	5A11	Terminated	[5]
2-chloro-5-nitro-N-phenylbenzamide	DMUGQIV	Discovery agent	N.A.	Investigative	[6]
LG100754	DMEK4FY	Discovery agent	N.A.	Investigative	[7]
L-796449	DMWTGQM	Discovery agent	N.A.	Investigative	[8]
L-165461	DMKBSGN	Discovery agent	N.A.	Investigative	[8]
AD-5061	DM5WV13	Discovery agent	N.A.	Investigative	[9]
TZD18	DMVCHOX	Discovery agent	N.A.	Investigative	[10]
(9Z,12E)-12-nitrooctadeca-9,12-dienoic acid	DM2REIN	Discovery agent	N.A.	Investigative	[11]
reglitazar	DMQ3ER0	Discovery agent	N.A.	Investigative	[12]

Drug(s) Targeting Oxysterols receptor LXR-beta (NR1H2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
VTB-38543	DMNY3J0	Atopic dermatitis	EA80	Phase 2	[13]
2-Propanol, Isopropanol	DML5O0H	Discovery agent	N.A.	Investigative	[14]
Desmosterol	DMV8SUM	Discovery agent	N.A.	Investigative	[15]
WAY-214950	DM8ODI7	Discovery agent	N.A.	Investigative	[16]
27-hydroxycholesterol	DM2L6OZ	Discovery agent	N.A.	Investigative	[17]
22R-hydroxycholesterol	DME8273	Discovery agent	N.A.	Investigative	[18]
GSK-9772	DM4WS3R	Discovery agent	N.A.	Investigative	[19]
Riccardin C	DM6MYGX	Discovery agent	N.A.	Investigative	[20]
2-benzyl-4,5,6,7-tetrachloroisoindoline-1,3-dione	DMH76SO	Discovery agent	N.A.	Investigative	[21]
AZ12260493	DMQ5H2V	Discovery agent	N.A.	Investigative	[22]

Drug(s) Targeting Peroxisome proliferator-activated receptor delta (PPARD)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GFT-505	DM7ZOAE	Non-alcoholic steatohepatitis	DB92.1	Phase 3	[23]
MBX-8025	DMNTCV4	Obesity	5B81	Phase 2/3	[24]
T3D-959	DM1FY97	Alzheimer disease	8A20	Phase 1/2	[25]
KD3010	DMNFDYE	Metabolic disorder	5C50-5D2Z	Phase 1	[26]
SAR351034	DM15PG9	Dyslipidemia	5C80-5C81	Phase 1	[27]
CER-002	DMLBKZV	Dyslipidemia	5C80-5C81	Phase 1	[28]
PMID25416646-Compound-Figure5-C	DM17FKL	N. A.	N. A.	Patented	[29]
GW-501516	DMPL2KM	Type-1 diabetes	5A10	Discontinued in Phase 4	[30]
Sodelglitazar	DMJ816F	Hyperlipidaemia	5C80	Discontinued in Phase 2	[31]
Indeglitazar	DMS56UD	Type-2 diabetes	5A11	Discontinued in Phase 2	[32]

Drug(s) Targeting Oxysterols receptor LXR-alpha (NR1H3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
US9073931, E2	DMK9FJG	N. A.	N. A.	Patented	[33]
BDBM50177019	DMEL28G	N. A.	N. A.	Patented	[34]
US9006244, E2b	DMP0TBO	N. A.	N. A.	Patented	[35]
US9073931, E1	DM2Z43I	N. A.	N. A.	Patented	[33]
US9006244, E1	DMBF1C0	N. A.	N. A.	Patented	[35]
BDBM50177012	DM52IQF	N. A.	N. A.	Patented	[34]
US9006244, E2a	DMPDF9B	N. A.	N. A.	Patented	[35]
67S	DMJL1MB	N. A.	N. A.	Patented	[34]
US9073931, E3	DMCYM8P	N. A.	N. A.	Patented	[33]
Desmosterol	DMV8SUM	Discovery agent	N.A.	Investigative	[15]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Oxysterols receptor LXR-alpha (NR1H3)	TTECBXN	NR1H3_HUMAN	Agonist	[2]
Oxysterols receptor LXR-beta (NR1H2)	TTXA6PH	NR1H2_HUMAN	Agonist	[2]
Peroxisome proliferator-activated receptor delta (PPARD)	TT2JWF6	PPARD_HUMAN	Agonist	[3]
PPAR-gamma messenger RNA (PPARG mRNA)	TTT2SVW	PPARG_HUMAN	Agonist	[3]

References

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• [2] A novel liver X receptor agonist establishes species differences in the regulation of cholesterol 7alpha-hydroxylase (CYP7a). Endocrinology. 2002 Jul;143(7):2548-58.
• [3] Novel peroxisome proliferator-activated receptor (PPAR) gamma and PPARdelta ligands produce distinct biological effects. J Biol Chem. 1999 Mar 5;274(10):6718-25.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] Phenylacetic acid derivatives as hPPAR agonists. Bioorg Med Chem Lett. 2003 Apr 7;13(7):1277-80.
• [9] A novel oxyiminoalkanoic acid derivative, TAK-559, activates human peroxisome proliferator-activated receptor subtypes. Eur J Pharmacol. 2004 Jul 8;495(1):17-26.
• [10] A novel peroxisome proliferator-activated receptor alpha/gamma dual agonist demonstrates favorable effects on lipid homeostasis. Endocrinology. 2004 Apr;145(4):1640-8.
• [11] 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.
• [12] Pharmacological profiles of a novel oral antidiabetic agent, JTT-501, an isoxazolidinedione derivative. Eur J Pharmacol. 1999 Jan 8;364(2-3):211-9.
• [13] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [14] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [15] Sterol intermediates from cholesterol biosynthetic pathway as liver X receptor ligands. J Biol Chem. 2006 Sep 22;281(38):27816-26.
• [16] Indazole-based liver X receptor (LXR) modulators with maintained atherosclerotic lesion reduction activity but diminished stimulation of hepatic tr... J Med Chem. 2008 Nov 27;51(22):7161-8.
• [17] 27-hydroxycholesterol is an endogenous ligand for liver X receptor in cholesterol-loaded cells. J Biol Chem. 2001 Oct 19;276(42):38378-87.
• [18] An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature. 1996 Oct 24;383(6602):728-31.
• [19] Structure-guided design of N-phenyl tertiary amines as transrepression-selective liver X receptor modulators with anti-inflammatory activity. J Med Chem. 2008 Sep 25;51(18):5758-65.
• [20] Co-existence of alpha-glucosidase-inhibitory and liver X receptor-regulatory activities and their separation by structural development. Bioorg Med Chem. 2008 Apr 15;16(8):4272-85.
• [21] Liver X receptor antagonists with a phthalimide skeleton derived from thalidomide-related glucosidase inhibitors. Bioorg Med Chem Lett. 2007 Jul 15;17(14):3957-61.
• [22] 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. (Target id: 601).
• [23] Dual peroxisome proliferator-activated receptor / agonist GFT505 improves hepatic and peripheral insulin sensitivity in abdominally obese subjects.Diabetes Care.2013 Oct;36(10):2923-30.
• [24] ClinicalTrials.gov (NCT00701883) Safety and Benefit of MBX-8025 With and Without Commonly Used Statins in Moderately Overweight Patients With High Cholesterol. U. S. National Institute of Health. 2008.
• [25] Phrma report (2013 Alzheimers disease)
• [26] Kalypsys nearing completion of phase Ia study of KD3010 for metabolic disorders. Kalypsys. 2007.
• [27] Addressing Unmet Medical Needs in Type 2 Diabetes: A Narrative Review of Drugs under Development. Curr Diabetes Rev. 2015 March; 11(1): 17-31.
• [28] Fibrates, glitazones, and peroxisome proliferator-activated receptors. Arterioscler Thromb Vasc Biol. 2010 May; 30(5): 894-899.
• [29] PPAR ligands and their therapeutic applications: a patent review (2008 - 2014).Expert Opin Ther Pat. 2015 Feb;25(2):175-91.
• [30] Lipid effects of peroxisome proliferator-activated receptor- agonist GW501516 in subjects with low high-density lipoprotein cholesterol: characteristics of metabolic syndrome.Arterioscler Thromb Vasc Biol.2012 Sep;32(9):2289-94.
• [31] Docking and molecular dynamics simulations of peroxisome proliferator activated receptors interacting with pan agonist sodelglitazar. Protein Pept Lett. 2011 Oct;18(10):1021-7.
• [32] Scaffold-based discovery of indeglitazar, a PPAR pan-active anti-diabetic agent. Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):262-7.
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• [35] Liver X receptor modulators. US9006244.