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

General Information of Drug (ID: DMKDLB7)

• Drug Name: GSK-3787 Drug Info
• Synonyms: GSK3787; 188591-46-0; GSK 3787; GSK-3787; 4-Chloro-N-[2-[[5-(trifluoromethyl)-2-pyridinyl]sulfonyl]ethyl]benzamide; CHEMBL598608; 4-Chloro-N-(2-{[5-trifluoromethyl)-2-pyridyl]sulfonyl}ethyl)benzamide; 4-chloro-N-[2-[5-(trifluoromethyl)pyridin-2-yl]sulfonylethyl]benzamide; Benzamide, 4-chloro-N-[2-[[5-(trifluoromethyl)-2-pyridinyl]sulfonyl]ethyl]-; Maybridge3_000547; AC1MCTIO; C15H12ClF3N2O3S; MLS006012025; SCHEMBL14968834; CTK8E8261; KS-00000XJC; AOB6285; QCR-146; EX-A704; DTXSID00384175; MolPort-002-892-395; HMS1432I19

Indication

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

• Cross-matching ID:
  PubChem CID: 2800647
  CAS Number: CAS 188591-46-0
  TTD Drug ID: DMKDLB7

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	[3]
MBX-8025	DMNTCV4	Obesity	5B81	Phase 2/3	[4]
T3D-959	DMR3245	Alzheimer disease	8A20	Phase 2	[5]
T3D-959	DMR3245	Alzheimer disease	8A20	Phase 2	[6]
KD3010	DMNFDYE	Metabolic disorder	5C50-5D2Z	Phase 1	[7]
SAR351034	DM15PG9	Dyslipidemia	5C80-5C81	Phase 1	[8]
CER-002	DMLBKZV	Dyslipidemia	5C80-5C81	Phase 1	[9]
PMID25416646-Compound-Figure5-C	DM17FKL	N. A.	N. A.	Patented	[10]
GW-501516	DMPL2KM	Type-1 diabetes	5A10	Discontinued in Phase 4	[11]
Sodelglitazar	DMJ816F	Hyperlipidaemia	5C80	Discontinued in Phase 2	[12]

Drug(s) Affected By Carnitine O-palmitoyltransferase 1, liver isoform (CPT1A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Clofibrate	DMPC1J7	Dysbetalipoproteinemia	5C80.2	Approved	[13]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[14]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[15]
obeticholic acid	DM3Q1SM	Primary biliary cholangitis	DB96.1	Approved	[16]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[17]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[18]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[19]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[20]
Liothyronine	DM6IR3P	Congenital hypothyroidism		Approved	[21]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[22]

Drug(s) Affected By kinase isozyme 4, mitochondrial (PDK4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Quercetin	DM3NC4M	Obesity	5B81	Approved	[23]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[24]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[25]
Liothyronine	DM6IR3P	Congenital hypothyroidism		Approved	[21]
Ibuprofen	DM8VCBE	Dysmenorrhea	GA34.3	Approved	[26]
Clodronate	DM9Y6X7	Hypercalcaemia	5B91.0	Approved	[26]
Cidofovir	DMA13GD	Cytomegalovirus infection	1D82	Approved	[26]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[27]
Testosterone enanthate	DMB6871	N. A.	N. A.	Approved	[28]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[29]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Peroxisome proliferator-activated receptor delta (PPARD)	TT2JWF6	PPARD_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Carnitine O-palmitoyltransferase 1, liver isoform (CPT1A)	OTI862QH	CPT1A_HUMAN	Gene/Protein Processing	[2]
kinase isozyme 4, mitochondrial (PDK4)	OTCMHMBZ	PDK4_HUMAN	Gene/Protein Processing	[2]

References

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• [3] 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.
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• [5] Phrma report (2013 Alzheimers disease)
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• [8] Addressing Unmet Medical Needs in Type 2 Diabetes: A Narrative Review of Drugs under Development. Curr Diabetes Rev. 2015 March; 11(1): 17-31.
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• [10] PPAR ligands and their therapeutic applications: a patent review (2008 - 2014).Expert Opin Ther Pat. 2015 Feb;25(2):175-91.
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• [12] Docking and molecular dynamics simulations of peroxisome proliferator activated receptors interacting with pan agonist sodelglitazar. Protein Pept Lett. 2011 Oct;18(10):1021-7.
• [13] Positive regulation of hepatic carnitine palmitoyl transferase 1A (CPT1A) activities by soy isoflavones and L-carnitine. Eur J Nutr. 2006 Mar;45(3):159-64. doi: 10.1007/s00394-005-0576-5. Epub 2005 Dec 20.
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• [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] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [17] Species-specific toxicity of diclofenac and troglitazone in primary human and rat hepatocytes. Chem Biol Interact. 2009 Apr 15;179(1):17-24.
• [18] 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.
• [19] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [20] Aspirin regulates hepatocellular lipid metabolism by activating AMPK signaling pathway. J Toxicol Sci. 2015 Feb;40(1):127-36. doi: 10.2131/jts.40.127.
• [21] Role of sirtuin 1 in the regulation of hepatic gene expression by thyroid hormone. J Biol Chem. 2013 Jan 11;288(2):807-18. doi: 10.1074/jbc.M112.437970. Epub 2012 Dec 3.
• [22] JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
• [23] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [24] The PPAR gamma agonist troglitazone induces musclin mRNA expression in human myotubes. Horm Metab Res. 2006 Sep;38(9):614-6. doi: 10.1055/s-2006-951310.
• [25] Retinoic acids and trichostatin A (TSA), a histone deacetylase inhibitor, induce human pyruvate dehydrogenase kinase 4 (PDK4) gene expression. Biochim Biophys Acta. 2006 Mar-Apr;1759(3-4):141-51. doi: 10.1016/j.bbaexp.2006.04.005. Epub 2006 Apr 27.
• [26] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [27] 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.
• [28] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [29] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.