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

General Information of Drug (ID: DMBM2I9)

• Drug Name: LY-518674 Drug Info
• Synonyms: LY-674; 2-Methyl-2-[4-[3-[1-(4-methylbenzyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl]propyl]phenoxy]propionic acid

Indication

Disease Entry	ICD 11	Status	REF
Diabetic complication	5A2Y	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 135449333
  ChEBI ID: CHEMBL424133
  CAS Number: CAS 425671-29-0
  TTD Drug ID: DMBM2I9

Molecule-Related Drug Atlas

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	[4]
Fenofibrate	DMFKXDY	Coronary atherosclerosis		Approved	[5]
Bezafibrate	DMZDCS0	Hypercholesterolaemia	5C80.0	Approved	[6]
Ciprofibrate	DMGC5DB	Hyperlipoproteinemia	5C80	Approved	[5]
Pemafibrate	DMD1VZL	Hyperlipidemia	5C80.Z	Approved	[7]
MURAGLITAZAR	DMG3NFZ	N. A.	N. A.	Phase 3	[8]
Ragaglitazar	DMFSHEM	Type-1 diabetes	5A10	Phase 3	[9]
CS-038	DM67P0F	Type-2 diabetes	5A11	Phase 3	[10]
TESAGLITAZAR	DMGRBN5	Type-1 diabetes	5A10	Phase 3	[11]
GFT-505	DM7ZOAE	Non-alcoholic steatohepatitis	DB92.1	Phase 3	[12]

Drug(s) Affected By Phospholipid-transporting ATPase ABCA1 (ABCA1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[13]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[14]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[15]
Fluoxetine	DM3PD2C	Bipolar depression		Approved	[16]
obeticholic acid	DM3Q1SM	Primary biliary cholangitis	DB96.1	Approved	[17]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[18]
Omeprazole	DM471KJ	Cystic fibrosis	CA25	Approved	[19]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[20]
Rifampicin	DM5DSFZ	Non-insulin dependent diabetes	5A11	Approved	[21]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[22]

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	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Phospholipid-transporting ATPase ABCA1 (ABCA1)	OT94G6BQ	ABCA1_HUMAN	Gene/Protein Processing	[3]

References

• [1] 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. (Ligand id: 2658).
• [2] Potent and selective PPAR-alpha agonist LY518674 upregulates both ApoA-I production and catabolism in human subjects with the metabolic syndrome. Arterioscler Thromb Vasc Biol. 2009 Jan;29(1):140-6.
• [3] On the mechanism for PPAR agonists to enhance ABCA1 gene expression. Atherosclerosis. 2009 Aug;205(2):413-9. doi: 10.1016/j.atherosclerosis.2009.01.008. Epub 2009 Jan 19.
• [4] 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.
• [5] Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity. J Biol Chem. 2000 Jun 2;275(22):16638-42.
• [6] 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.
• [7] Pemafibrate: First Global Approval. Drugs. 2017 Oct;77(16):1805-1810.
• [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] 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.
• [10] 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.
• [11] Tesaglitazar, a dual PPAR-/ agonist, hamster carcinogenicity, investigative animal and clinical studies.Toxicol Pathol.2012;40(1):18-32.
• [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] Atheroprotective effects of methotrexate on reverse cholesterol transport proteins and foam cell transformation in human THP-1 monocyte/macrophages. Arthritis Rheum. 2008 Dec;58(12):3675-83.
• [14] Combining simvastatin with the farnesyltransferase inhibitor tipifarnib results in an enhanced cytotoxic effect in a subset of primary CD34+ acute myeloid leukemia samples. Clin Cancer Res. 2009 May 1;15(9):3076-83. doi: 10.1158/1078-0432.CCR-08-3004. Epub 2009 Apr 21.
• [15] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [16] Screening autism-associated environmental factors in differentiating human neural progenitors with fractional factorial design-based transcriptomics. Sci Rep. 2023 Jun 29;13(1):10519. doi: 10.1038/s41598-023-37488-0.
• [17] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [18] 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.
• [19] Proton pump inhibitor lansoprazole is a nuclear liver X receptor agonist. Biochem Pharmacol. 2010 May 1;79(9):1310-6. doi: 10.1016/j.bcp.2009.12.018. Epub 2010 Jan 8.
• [20] Repression of hepatocyte nuclear factor 4 alpha by AP-1 underlies dyslipidemia associated with retinoic acid. J Lipid Res. 2019 Apr;60(4):794-804. doi: 10.1194/jlr.M088880. Epub 2019 Feb 1.
• [21] Pregnane X receptor-agonists down-regulate hepatic ATP-binding cassette transporter A1 and scavenger receptor class B type I. Biochem Biophys Res Commun. 2005 Jun 17;331(4):1533-41. doi: 10.1016/j.bbrc.2005.04.071.
• [22] Inhibition of liver x receptor/retinoid X receptor-mediated transcription contributes to the proatherogenic effects of arsenic in macrophages in vitro. Arterioscler Thromb Vasc Biol. 2010 Jun;30(6):1228-36. doi: 10.1161/ATVBAHA.110.205500. Epub 2010 Mar 25.