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

General Information of Drug (ID: DM5WRJX)

• Drug Name: GSK-677954 Drug Info
• Synonyms: SCHEMBL2065429

Indication

Disease Entry	ICD 11	Status	REF
Non-alcoholic fatty liver disease	DB92	Discontinued in Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 56603715
  TTD Drug ID: DM5WRJX

Molecule-Related Drug Atlas

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	[2]
MBX-8025	DMNTCV4	Obesity	5B81	Phase 2/3	[3]
T3D-959	DMR3245	Alzheimer disease	8A20	Phase 2	[4]
T3D-959	DMR3245	Alzheimer disease	8A20	Phase 2	[5]
KD3010	DMNFDYE	Metabolic disorder	5C50-5D2Z	Phase 1	[6]
SAR351034	DM15PG9	Dyslipidemia	5C80-5C81	Phase 1	[7]
CER-002	DMLBKZV	Dyslipidemia	5C80-5C81	Phase 1	[8]
PMID25416646-Compound-Figure5-C	DM17FKL	N. A.	N. A.	Patented	[9]
GW-501516	DMPL2KM	Type-1 diabetes	5A10	Discontinued in Phase 4	[10]
Sodelglitazar	DMJ816F	Hyperlipidaemia	5C80	Discontinued in Phase 2	[11]

Drug(s) Targeting Peroxisome proliferator-activated receptor gamma (PPAR-gamma)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[12]
Pioglitazone	DMKJ485	Amyotrophic lateral sclerosis	8B60.0	Approved	[13]
Lobeglitazone	DMHY3IP	Type-2 diabetes	5A11	Approved	[14]
Rosiglitazone XR	DMT45MU	Type-2 diabetes	5A11	Approved	[15]
Thiazolidinedione	DMC1NBW	Alzheimer disease	8A20	Approved	[13]
Glitazone	DMDN4A1	N. A.	N. A.	Phase 4	[16]
MURAGLITAZAR	DMG3NFZ	N. A.	N. A.	Phase 3	[17]
Rivoglitazone	DMBY31K	Ocular inflammation	9C61.24	Phase 3	[18]
Balaglitazone	DMXBHR6	Type-1 diabetes	5A10	Phase 3	[19]
Ragaglitazar	DMFSHEM	Type-1 diabetes	5A10	Phase 3	[20]

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	[14]
Fenofibrate	DMFKXDY	Coronary atherosclerosis		Approved	[16]
Bezafibrate	DMZDCS0	Hypercholesterolaemia	5C80.0	Approved	[21]
Ciprofibrate	DMGC5DB	Hyperlipoproteinemia	5C80	Approved	[16]
Pemafibrate	DMD1VZL	Hyperlipidemia	5C80.Z	Approved	[22]
MURAGLITAZAR	DMG3NFZ	N. A.	N. A.	Phase 3	[17]
Ragaglitazar	DMFSHEM	Type-1 diabetes	5A10	Phase 3	[20]
CS-038	DM67P0F	Type-2 diabetes	5A11	Phase 3	[23]
TESAGLITAZAR	DMGRBN5	Type-1 diabetes	5A10	Phase 3	[24]
GFT-505	DM7ZOAE	Non-alcoholic steatohepatitis	DB92.1	Phase 3	[2]

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]

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] T3D-959: A Multi-Faceted Disease Remedial Drug Candidate for the Treatment of Alzheimer's Disease. J Alzheimers Dis. 2016;51(1):123-38.
• [6] Kalypsys nearing completion of phase Ia study of KD3010 for metabolic disorders. Kalypsys. 2007.
• [7] Addressing Unmet Medical Needs in Type 2 Diabetes: A Narrative Review of Drugs under Development. Curr Diabetes Rev. 2015 March; 11(1): 17-31.
• [8] Fibrates, glitazones, and peroxisome proliferator-activated receptors. Arterioscler Thromb Vasc Biol. 2010 May; 30(5): 894-899.
• [9] PPAR ligands and their therapeutic applications: a patent review (2008 - 2014).Expert Opin Ther Pat. 2015 Feb;25(2):175-91.
• [10] 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.
• [11] Docking and molecular dynamics simulations of peroxisome proliferator activated receptors interacting with pan agonist sodelglitazar. Protein Pept Lett. 2011 Oct;18(10):1021-7.
• [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] 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.
• [21] 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.
• [22] Pemafibrate: First Global Approval. Drugs. 2017 Oct;77(16):1805-1810.
• [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.