Details of the Drug

General Information of Drug (ID: DM5WRJX)

Drug Name
GSK-677954
Synonyms SCHEMBL2065429
Indication
Disease Entry ICD 11 Status REF
Non-alcoholic fatty liver disease DB92 Discontinued in Phase 2 [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 4 Molecular Weight (mw) 671.8
Topological Polar Surface Area (xlogp) 8.8
Rotatable Bond Count (rotbonds) 12
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 12
Chemical Identifiers
Formula
C34H36F3N3O4S2
IUPAC Name
2-ethyl-2-[4-[[4-[4-(4-methoxyphenyl)piperazin-1-yl]-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenoxy]butanoic acid
Canonical SMILES
CCC(CC)(C(=O)O)OC1=CC=C(C=C1)SCC2=C(N=C(S2)C3=CC=C(C=C3)C(F)(F)F)N4CCN(CC4)C5=CC=C(C=C5)OC
InChI
InChI=1S/C34H36F3N3O4S2/c1-4-33(5-2,32(41)42)44-27-14-16-28(17-15-27)45-22-29-30(38-31(46-29)23-6-8-24(9-7-23)34(35,36)37)40-20-18-39(19-21-40)25-10-12-26(43-3)13-11-25/h6-17H,4-5,18-22H2,1-3H3,(H,41,42)
InChIKey
COHCTXOFKQXTRQ-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
56603715
TTD ID
D0S6KX

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 Agonist [1]
Peroxisome proliferator-activated receptor delta (PPARD) TT2JWF6 PPARD_HUMAN Agonist [1]
Peroxisome proliferator-activated receptor gamma (PPAR-gamma) TTZMAO3 PPARG_HUMAN Agonist [1]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Non-alcoholic fatty liver disease
ICD Disease Classification DB92
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Peroxisome proliferator-activated receptor gamma (PPAR-gamma) DTT PPARG 2.41E-01 -0.06 -0.25
Peroxisome proliferator-activated receptor delta (PPARD) DTT PPARD 3.78E-01 9.87E-03 0.06
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 Emerging drugs for non-alcoholic fatty liver disease. Expert Opin Emerg Drugs. 2008 Mar;13(1):145-58.
2 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.
3 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.
4 Phrma report (2013 Alzheimers disease)
5 Kalypsys nearing completion of phase Ia study of KD3010 for metabolic disorders. Kalypsys. 2007.
6 Addressing Unmet Medical Needs in Type 2 Diabetes: A Narrative Review of Drugs under Development. Curr Diabetes Rev. 2015 March; 11(1): 17-31.
7 Fibrates, glitazones, and peroxisome proliferator-activated receptors. Arterioscler Thromb Vasc Biol. 2010 May; 30(5): 894-899.
8 PPAR ligands and their therapeutic applications: a patent review (2008 - 2014).Expert Opin Ther Pat. 2015 Feb;25(2):175-91.
9 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.
10 Docking and molecular dynamics simulations of peroxisome proliferator activated receptors interacting with pan agonist sodelglitazar. Protein Pept Lett. 2011 Oct;18(10):1021-7.
11 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.
12 Expression of peroxisome proliferator-activated receptors (PPARs) in human urinary bladder carcinoma and growth inhibition by its agonists. Int J Cancer. 2003 May 1;104(5):597-602.
13 Functional PPAR-gamma receptor is a novel therapeutic target for ACTH-secreting pituitary adenomas. Nat Med. 2002 Nov;8(11):1281-7.
14 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.
15 Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
16 Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity. J Biol Chem. 2000 Jun 2;275(22):16638-42.
17 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.
18 A randomized-controlled trial to investigate the effects of rivoglitazone, a novel PPAR gamma agonist on glucose-lipid control in type 2 diabetes. Diabetes Obes Metab. 2011 Sep;13(9):806-13.
19 Balaglitazone: a second generation peroxisome proliferator-activated receptor (PPAR) gamma () agonist.Mini Rev Med Chem.2012 Feb;12(2):87-97.
20 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.
21 Pemafibrate: First Global Approval. Drugs. 2017 Oct;77(16):1805-1810.
22 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.
23 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.
24 Tesaglitazar, a dual PPAR-/ agonist, hamster carcinogenicity, investigative animal and clinical studies.Toxicol Pathol.2012;40(1):18-32.