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

General Information of Drug (ID: DMM8V9E)

• Drug Name: GW-2331 Drug Info
• Synonyms: 190844-95-2; PPAR ligand, Glaxo Wellcome

Indication

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

• Cross-matching ID:
  PubChem CID: 657048
  TTD Drug ID: DMM8V9E

Molecule-Related Drug Atlas

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	[3]
Pioglitazone	DMKJ485	Amyotrophic lateral sclerosis	8B60.0	Approved	[4]
Lobeglitazone	DMHY3IP	Type-2 diabetes	5A11	Approved	[5]
Rosiglitazone XR	DMT45MU	Type-2 diabetes	5A11	Approved	[6]
Thiazolidinedione	DMC1NBW	Alzheimer disease	8A20	Approved	[4]
Glitazone	DMDN4A1	N. A.	N. A.	Phase 4	[7]
MURAGLITAZAR	DMG3NFZ	N. A.	N. A.	Phase 3	[8]
Rivoglitazone	DMBY31K	Ocular inflammation	9C61.24	Phase 3	[9]
Balaglitazone	DMXBHR6	Type-1 diabetes	5A10	Phase 3	[10]
Ragaglitazar	DMFSHEM	Type-1 diabetes	5A10	Phase 3	[11]

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	[5]
Fenofibrate	DMFKXDY	Coronary atherosclerosis		Approved	[7]
Bezafibrate	DMZDCS0	Hypercholesterolaemia	5C80.0	Approved	[12]
Ciprofibrate	DMGC5DB	Hyperlipoproteinemia	5C80	Approved	[7]
Pemafibrate	DMD1VZL	Hyperlipidemia	5C80.Z	Approved	[13]
MURAGLITAZAR	DMG3NFZ	N. A.	N. A.	Phase 3	[8]
Ragaglitazar	DMFSHEM	Type-1 diabetes	5A10	Phase 3	[11]
CS-038	DM67P0F	Type-2 diabetes	5A11	Phase 3	[14]
TESAGLITAZAR	DMGRBN5	Type-1 diabetes	5A10	Phase 3	[15]
GFT-505	DM7ZOAE	Non-alcoholic steatohepatitis	DB92.1	Phase 3	[16]

Drug(s) Affected By Fatty acid-binding protein, adipocyte (FABP4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Rofecoxib	DM3P5DA	Osteoarthritis	FA00-FA05	Approved	[17]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[18]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[19]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[20]
Ibuprofen	DM8VCBE	Dysmenorrhea	GA34.3	Approved	[17]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[21]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[22]
Ursodeoxycholic acid	DMCUT21	Cholelithiasis	DC11	Approved	[23]
Fenofibrate	DMFKXDY	Coronary atherosclerosis		Approved	[24]
Capsaicin	DMGMF6V	Back pain	ME84.Z	Approved	[25]

Drug(s) Affected By Peroxisome proliferator-activated receptor gamma (PPARG)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[26]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[27]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[28]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[18]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[29]
Glucosamine	DM4ZLFD	Osteoarthritis	FA00-FA05	Approved	[30]
Isoniazid	DM5JVS3	Latent tuberculosis infection		Approved	[31]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[32]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[33]
Stavudine	DM6DEK9	Human immunodeficiency virus infection	1C62	Approved	[34]

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	Modulator	[1]
Peroxisome proliferator-activated receptor gamma (PPAR-gamma)	TTZMAO3	PPARG_HUMAN	Modulator	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Fatty acid-binding protein, adipocyte (FABP4)	OT3DKFOU	FABP4_HUMAN	Gene/Protein Processing	[2]
Peroxisome proliferator-activated receptor gamma (PPARG)	OTHMARHO	PPARG_HUMAN	Gene/Protein Processing	[2]

References

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• [2] Human adipocyte fatty acid-binding protein (aP2) gene promoter-driven reporter assay discriminates nonlipogenic peroxisome proliferator-activated receptor gamma ligands. J Pharmacol Exp Ther. 2004 Nov;311(2):467-75. doi: 10.1124/jpet.104.068254. Epub 2004 Jul 23.
• [3] 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.
• [4] Functional PPAR-gamma receptor is a novel therapeutic target for ACTH-secreting pituitary adenomas. Nat Med. 2002 Nov;8(11):1281-7.
• [5] 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.
• [6] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [7] Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity. J Biol Chem. 2000 Jun 2;275(22):16638-42.
• [8] 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.
• [9] 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.
• [10] Balaglitazone: a second generation peroxisome proliferator-activated receptor (PPAR) gamma () agonist.Mini Rev Med Chem.2012 Feb;12(2):87-97.
• [11] 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.
• [12] 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.
• [13] Pemafibrate: First Global Approval. Drugs. 2017 Oct;77(16):1805-1810.
• [14] 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.
• [15] Tesaglitazar, a dual PPAR-/ agonist, hamster carcinogenicity, investigative animal and clinical studies.Toxicol Pathol.2012;40(1):18-32.
• [16] 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.
• [17] Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain. Pain. 2007 Mar;128(1-2):136-47.
• [18] Induction of solid tumor differentiation by the peroxisome proliferator-activated receptor-gamma ligand troglitazone in patients with liposarcoma. Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3951-6. doi: 10.1073/pnas.96.7.3951.
• [19] Retinoic acid-induced downmodulation of telomerase activity in human cancer cells. Exp Mol Pathol. 2005 Oct;79(2):108-17.
• [20] Adipocyte differentiation, mitochondrial gene expression and fat distribution: differences between zidovudine and tenofovir after 6 months. Antivir Ther. 2009;14(8):1089-100. doi: 10.3851/IMP1457.
• [21] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [22] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [23] Ursodeoxycholic acid but not tauroursodeoxycholic acid inhibits proliferation and differentiation of human subcutaneous adipocytes. PLoS One. 2013 Dec 3;8(12):e82086. doi: 10.1371/journal.pone.0082086. eCollection 2013.
• [24] Differential effects of peroxisome proliferator-activated receptor activators on the mRNA levels of genes involved in lipid metabolism in primary human monocyte-derived macrophages. Metabolism. 2003 May;52(5):652-7. doi: 10.1053/meta.2003.50100.
• [25] Induction of the endoplasmic reticulum stress protein GADD153/CHOP by capsaicin in prostate PC-3 cells: a microarray study. Biochem Biophys Res Commun. 2008 Aug 8;372(4):785-91.
• [26] COX-2 and PPAR-gama confer cannabidiol-induced apoptosis of human lung cancer cells. Mol Cancer Ther. 2013 Jan;12(1):69-82.
• [27] Protective effects of myricitrin against osteoporosis via reducing reactive oxygen species and bone-resorbing cytokines. Toxicol Appl Pharmacol. 2014 Nov 1;280(3):550-60.
• [28] The effect of quercetin and kaempferol aglycones and glucuronides on peroxisome proliferator-activated receptor-gamma (PPAR-). Food Funct. 2015 Apr;6(4):1098-107. doi: 10.1039/c5fo00076a.
• [29] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [30] Glucosamine sulfate reduces prostaglandin E(2) production in osteoarthritic chondrocytes through inhibition of microsomal PGE synthase-1. J Rheumatol. 2012 Mar;39(3):635-44. doi: 10.3899/jrheum.110621. Epub 2011 Nov 15.
• [31] Isoniazid suppresses antioxidant response element activities and impairs adipogenesis in mouse and human preadipocytes. Toxicol Appl Pharmacol. 2013 Dec 15;273(3):435-41. doi: 10.1016/j.taap.2013.10.005. Epub 2013 Oct 12.
• [32] Regulatory role of KEAP1 and NRF2 in PPAR expression and chemoresistance in human non-small-cell lung carcinoma cells. Free Radic Biol Med. 2012 Aug 15;53(4):758-68. doi: 10.1016/j.freeradbiomed.2012.05.041. Epub 2012 Jun 7.
• [33] Aspirin inhibits MMP-9 mRNA expression and release via the PPARalpha/gamma and COX-2/mPGES-1-mediated pathways in macrophages derived from THP-1 cells. Biomed Pharmacother. 2010 Feb;64(2):118-23. doi: 10.1016/j.biopha.2009.04.033. Epub 2009 Oct 17.
• [34] Mitochondrial proliferation, DNA depletion and adipocyte differentiation in subcutaneous adipose tissue of HIV-positive HAART recipients. Antivir Ther. 2003 Aug;8(4):323-31.