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
CAS Number
CAS 425671-29-0
TTD Drug ID
DMBM2I9

Molecule-Related Drug Atlas

Molecule-Related Drug Atlas
Molecule Type:
DTT
DOT
Drug Status:
Approved Drug(s)
Clinical Trial Drug(s)
Download the Complete Related Drug List
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]
⏷ Show the Full List of 10 Drug(s)
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]
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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 [23]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [24]
Quercetin DM3NC4M Obesity 5B81 Approved [25]
Troglitazone DM3VFPD Diabetic complication 5A2Y Approved [26]
Tretinoin DM49DUI Acne vulgaris ED80 Approved [27]
Glucosamine DM4ZLFD Osteoarthritis FA00-FA05 Approved [28]
Isoniazid DM5JVS3 Latent tuberculosis infection Approved [29]
Arsenic trioxide DM61TA4 Acute lymphoblastic leukaemia 2A85 Approved [30]
Aspirin DM672AH Acute coronary syndrome BA41 Approved [31]
Stavudine DM6DEK9 Human immunodeficiency virus infection 1C62 Approved [32]
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Drug(s) Affected By Oxysterols receptor LXR-beta (NR1H2)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Tretinoin DM49DUI Acne vulgaris ED80 Approved [33]
Arsenic trioxide DM61TA4 Acute lymphoblastic leukaemia 2A85 Approved [34]
Ezetimibe DM7A8TW Atherosclerosis BD40 Approved [35]
Valproate DMCFE9I Epilepsy 8A60-8A68 Approved [36]
Gemfibrozil DMD8Q3J Hyperlipidaemia 5C80 Approved [3]
Fenofibrate DMFKXDY Coronary atherosclerosis Approved [3]
Bosentan DMIOGBU Pulmonary arterial hypertension BB01.0 Approved [37]
Temozolomide DMKECZD Adenocarcinoma 2D40 Approved [38]
Pioglitazone DMKJ485 Amyotrophic lateral sclerosis 8B60.0 Approved [3]
Etoposide DMNH3PG Acute myelogenous leukaemia 2A41 Approved [39]
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Drug(s) Affected By Peroxisome proliferator-activated receptor delta (PPARD)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [40]
Sulindac DM2QHZU Acute myelogenous leukaemia 2A41 Approved [41]
Methotrexate DM2TEOL Anterior urethra cancer Approved [42]
Tretinoin DM49DUI Acne vulgaris ED80 Approved [43]
Aspirin DM672AH Acute coronary syndrome BA41 Approved [44]
Hydroquinone DM6AVR4 Melasma ED60.1 Approved [45]
Marinol DM70IK5 Anorexia nervosa cachexia 6B80 Approved [46]
Calcitriol DM8ZVJ7 Congenital alopecia LC30 Approved [47]
Ciclosporin DMAZJFX Graft-versus-host disease 4B24 Approved [48]
Valproate DMCFE9I Epilepsy 8A60-8A68 Approved [49]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Affected By Oxysterols receptor LXR-alpha (NR1H3)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Tretinoin DM49DUI Acne vulgaris ED80 Approved [50]
Ciclosporin DMAZJFX Graft-versus-host disease 4B24 Approved [48]
Valproate DMCFE9I Epilepsy 8A60-8A68 Approved [49]
Gemfibrozil DMD8Q3J Hyperlipidaemia 5C80 Approved [3]
Ethanol DMDRQZU Chronic pain MG30 Approved [51]
Fenofibrate DMFKXDY Coronary atherosclerosis Approved [3]
Rosiglitazone DMILWZR Chronic kidney disease GB61 Approved [52]
Bosentan DMIOGBU Pulmonary arterial hypertension BB01.0 Approved [37]
Temozolomide DMKECZD Adenocarcinoma 2D40 Approved [38]
Pioglitazone DMKJ485 Amyotrophic lateral sclerosis 8B60.0 Approved [53]
⏷ Show the Full List of 10 Drug(s)

Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas
Download the Complete Interaction Atlas for Visualization in Cytoscape

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
Oxysterols receptor LXR-alpha (NR1H3) OT54YZ9I NR1H3_HUMAN Gene/Protein Processing [3]
Oxysterols receptor LXR-beta (NR1H2) OT4APA60 NR1H2_HUMAN Gene/Protein Processing [3]
Peroxisome proliferator-activated receptor delta (PPARD) OTI4WTOP PPARD_HUMAN Gene/Protein Processing [3]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Gene/Protein Processing [3]
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.
23 COX-2 and PPAR-gama confer cannabidiol-induced apoptosis of human lung cancer cells. Mol Cancer Ther. 2013 Jan;12(1):69-82.
24 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.
25 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.
26 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.
27 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.
28 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.
29 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.
30 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.
31 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.
32 Mitochondrial proliferation, DNA depletion and adipocyte differentiation in subcutaneous adipose tissue of HIV-positive HAART recipients. Antivir Ther. 2003 Aug;8(4):323-31.
33 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
34 Arsenic trioxide suppresses liver X receptor and enhances cholesteryl ester transfer protein expression without affecting the liver X receptor in HepG2 cells. Chem Biol Interact. 2016 Oct 25;258:288-96. doi: 10.1016/j.cbi.2016.09.009. Epub 2016 Sep 10.
35 Carotenoid transport is decreased and expression of the lipid transporters SR-BI, NPC1L1, and ABCA1 is downregulated in Caco-2 cells treated with ezetimibe. J Nutr. 2005 Oct;135(10):2305-12. doi: 10.1093/jn/135.10.2305.
36 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.
37 Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures. Arch Toxicol. 2018 Jun;92(6):1939-1952.
38 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
39 Regulation of Hepatic Cholesteryl Ester Transfer Protein Expression and Reverse Cholesterol Transport by Inhibition of DNA Topoisomerase II. J Biol Chem. 2015 Jun 5;290(23):14418-29. doi: 10.1074/jbc.M115.643015. Epub 2015 Apr 25.
40 Cannabidiol induces antioxidant pathways in keratinocytes by targeting BACH1. Redox Biol. 2020 Jan;28:101321. doi: 10.1016/j.redox.2019.101321. Epub 2019 Sep 5.
41 Functional characterization of peroxisome proliferator-activated receptor-/ expression in colon cancer. Mol Carcinog. 2011 Nov;50(11):884-900. doi: 10.1002/mc.20757. Epub 2011 Mar 11.
42 The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
43 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
44 Aspirin-induced apoptosis in jurkat cells is not mediated by peroxisome proliferator-activated receptor delta. Mol Cell Biochem. 2004 Nov;266(1-2):57-63. doi: 10.1023/b:mcbi.0000049138.67699.7b.
45 Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
46 (9)-Tetrahydrocannabinol upregulates fatty acid 2-hydroxylase (FA2H) via PPAR induction: A possible evidence for the cancellation of PPAR/-mediated inhibition of PPAR in MDA-MB-231?cells. Arch Biochem Biophys. 2019 Feb 15;662:219-225. doi: 10.1016/j.abb.2018.12.011. Epub 2018 Dec 13.
47 Cross-talk between vitamin D receptor (VDR)- and peroxisome proliferator-activated receptor (PPAR)-signaling in melanoma cells. Anticancer Res. 2009 Sep;29(9):3647-58.
48 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.
49 Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
50 Retinoic acid-induced downmodulation of telomerase activity in human cancer cells. Exp Mol Pathol. 2005 Oct;79(2):108-17.
51 The potential effects of HECTD4 variants on fasting glucose and triglyceride levels in relation to prevalence of type 2 diabetes based on alcohol intake. Arch Toxicol. 2022 Sep;96(9):2487-2499. doi: 10.1007/s00204-022-03325-y. Epub 2022 Jun 17.
52 Rosiglitazone upregulates caveolin-1 expression in THP-1 cells through a PPAR-dependent mechanism. J Lipid Res. 2004 Nov;45(11):2015-24. doi: 10.1194/jlr.M400049-JLR200. Epub 2004 Aug 16.
53 Comparison of the effects of pioglitazone and rosiglitazone on macrophage foam cell formation. Biochem Biophys Res Commun. 2004 Oct 22;323(3):782-8.