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

General Information of Drug (ID: DMWTGQM)

• Drug Name: L-796449 Drug Info
• Synonyms: L-796449; UNII-O937X0Z5EM; CHEMBL278994; O937X0Z5EM; 194608-80-5; KAPDPGZDHUCILF-UHFFFAOYSA-N; GTPL2689; SCHEMBL4296303; BDBM50085040; Benzeneacetic acid, 3-chloro-4-((3-((3-phenyl-7-propyl-6-benzofuranyl)oxy)propyl)thio)-; L796449; L 796449; L-796,449; 3-chloro-4-(3-(3-phenyl-7-propylbenzofuran-6-yloxy)propylthio)-phenylacetic acid; {3-Chloro-4-[3-(3-phenyl-7-propyl-benzofuran-6-yloxy)-propylsulfanyl]-phenyl}-acetic acid; 2-[3-chloro-4-[3-[(3-phenyl-7-propyl-1-benzofuran-6-yl)oxy]propylsulfanyl]phenyl]acetic acid

Indication

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

• Cross-matching ID:
  PubChem CID: 9891946
  CAS Number: CAS 194608-80-5
  TTD Drug ID: DMWTGQM

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	[3]
AD-5075	DM1SLJ9	Type-2 diabetes	5A11	Terminated	[4]
2-chloro-5-nitro-N-phenylbenzamide	DMUGQIV	Discovery agent	N.A.	Investigative	[5]
L-783483	DM6OTGE	Discovery agent	N.A.	Investigative	[6]
LG100754	DMEK4FY	Discovery agent	N.A.	Investigative	[7]
L-165461	DMKBSGN	Discovery agent	N.A.	Investigative	[2]
AD-5061	DM5WV13	Discovery agent	N.A.	Investigative	[8]
TZD18	DMVCHOX	Discovery agent	N.A.	Investigative	[9]
(9Z,12E)-12-nitrooctadeca-9,12-dienoic acid	DM2REIN	Discovery agent	N.A.	Investigative	[10]
reglitazar	DMQ3ER0	Discovery agent	N.A.	Investigative	[11]

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	[12]
MBX-8025	DMNTCV4	Obesity	5B81	Phase 2/3	[13]
T3D-959	DM1FY97	Alzheimer disease	8A20	Phase 1/2	[14]
KD3010	DMNFDYE	Metabolic disorder	5C50-5D2Z	Phase 1	[15]
SAR351034	DM15PG9	Dyslipidemia	5C80-5C81	Phase 1	[16]
CER-002	DMLBKZV	Dyslipidemia	5C80-5C81	Phase 1	[17]
PMID25416646-Compound-Figure5-C	DM17FKL	N. A.	N. A.	Patented	[18]
GW-501516	DMPL2KM	Type-1 diabetes	5A10	Discontinued in Phase 4	[19]
Sodelglitazar	DMJ816F	Hyperlipidaemia	5C80	Discontinued in Phase 2	[20]
Indeglitazar	DMS56UD	Type-2 diabetes	5A11	Discontinued in Phase 2	[21]

Drug(s) Targeting Peroxisome proliferator-activated receptor alpha (PPARA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lobeglitazone	DMHY3IP	Type-2 diabetes	5A11	Approved	[22]
Fenofibrate	DMFKXDY	High cholesterol level	5C80.0	Approved	[23]
Bezafibrate	DMZDCS0	Hyperlipidaemia	5C80	Approved	[24]
Ciprofibrate	DMGC5DB	Hyperlipoproteinemia	5C80	Approved	[23]
Pemafibrate	DMD1VZL	Hyperlipidemia	5C80.Z	Approved	[25]
Muraglitazar	DMG3NFZ	N. A.	N. A.	Phase 3	[26]
Ragaglitazar	DMFSHEM	Type-1 diabetes	5A10	Phase 3	[27]
CS-038	DM67P0F	Type-2 diabetes	5A11	Phase 3	[28]
TESAGLITAZAR	DMGRBN5	Type-1 diabetes	5A10	Phase 3	[29]
GFT-505	DM7ZOAE	Non-alcoholic steatohepatitis	DB92.1	Phase 3	[12]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Peroxisome proliferator-activated receptor alpha (PPARA)	TTJ584C	PPARA_HUMAN	Inhibitor	[2]
Peroxisome proliferator-activated receptor delta (PPARD)	TT2JWF6	PPARD_HUMAN	Inhibitor	[2]
PPAR-gamma messenger RNA (PPARG mRNA)	TTT2SVW	PPARG_HUMAN	Inhibitor	[2]

References

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• [2] Phenylacetic acid derivatives as hPPAR agonists. Bioorg Med Chem Lett. 2003 Apr 7;13(7):1277-80.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] Novel peroxisome proliferator-activated receptor (PPAR) gamma and PPARdelta ligands produce distinct biological effects. J Biol Chem. 1999 Mar 5;274(10):6718-25.
• [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] A novel oxyiminoalkanoic acid derivative, TAK-559, activates human peroxisome proliferator-activated receptor subtypes. Eur J Pharmacol. 2004 Jul 8;495(1):17-26.
• [9] A novel peroxisome proliferator-activated receptor alpha/gamma dual agonist demonstrates favorable effects on lipid homeostasis. Endocrinology. 2004 Apr;145(4):1640-8.
• [10] 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.
• [11] Pharmacological profiles of a novel oral antidiabetic agent, JTT-501, an isoxazolidinedione derivative. Eur J Pharmacol. 1999 Jan 8;364(2-3):211-9.
• [12] 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.
• [13] 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.
• [14] Phrma report (2013 Alzheimers disease)
• [15] Kalypsys nearing completion of phase Ia study of KD3010 for metabolic disorders. Kalypsys. 2007.
• [16] Addressing Unmet Medical Needs in Type 2 Diabetes: A Narrative Review of Drugs under Development. Curr Diabetes Rev. 2015 March; 11(1): 17-31.
• [17] Fibrates, glitazones, and peroxisome proliferator-activated receptors. Arterioscler Thromb Vasc Biol. 2010 May; 30(5): 894-899.
• [18] PPAR ligands and their therapeutic applications: a patent review (2008 - 2014).Expert Opin Ther Pat. 2015 Feb;25(2):175-91.
• [19] 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.
• [20] Docking and molecular dynamics simulations of peroxisome proliferator activated receptors interacting with pan agonist sodelglitazar. Protein Pept Lett. 2011 Oct;18(10):1021-7.
• [21] 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.
• [22] Tolerability and pharmacokinetics of lobeglitazone, a novel peroxisome proliferator-activated receptor-gamma agonist, after a single oral administration in healthy female subjects. Clin Drug Investig. 2014 Jul;34(7):467-74.
• [23] Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity. J Biol Chem. 2000 Jun 2;275(22):16638-42.
• [24] Bezafibrate at clinically relevant doses decreases serum/liver triglycerides via down-regulation of sterol regulatory element-binding protein-1c in... Mol Pharmacol. 2009 Apr;75(4):782-92.
• [25] Pemafibrate: First Global Approval. Drugs. 2017 Oct;77(16):1805-1810.
• [26] Muraglitazar, a dual (alpha/gamma) PPAR activator: a randomized, double-blind, placebo-controlled, 24-week monotherapy trial in adult patients with... Clin Ther. 2005 Aug;27(8):1181-95.
• [27] Ragaglitazar: the pharmacokinetics, pharmacodynamics, and tolerability of a novel dual PPAR alpha and gamma agonist in healthy subjects and patients with type 2 diabetes. J Clin Pharmacol. 2003 Nov;43(11):1244-56.
• [28] Determination of chiglitazar, a dual alpha/gamma peroxisome proliferator-activated receptor (PPAR) agonist, in human plasma by liquid chromatograph... Pharmazie. 2007 Nov;62(11):825-9.
• [29] Tesaglitazar, a dual PPAR-/ agonist, hamster carcinogenicity, investigative animal and clinical studies.Toxicol Pathol.2012;40(1):18-32.