Details of the Drug Combination

General Information of Drug Combination (ID: DCXOH42)

• Drug Combination Name: Fibrates + Sulfapyridine
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Fibrates (DMFNTMY): Small molecular drug
  Sulfapyridine (DMIUYFH): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 13.52
  Bliss Independence Score: 13.52
  Loewe Additivity Score: 27.34
  LHighest Single Agent (HSA) Score: 27.34

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Fibrates

Disease Entry	ICD 11	Status	REF
Dyslipidemia	5C80-5C81	Investigative	[2]

Fibrates Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Peroxisome proliferator-activated receptor alpha (PPARA)	TTJ584C	PPARA_HUMAN	Agonist	[2]

Fibrates Interacts with 13 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Peroxisome proliferator-activated receptor alpha (PPARA)	OTK095PP	PPARA_HUMAN	Affects Binding	[8]
Cytochrome P450 2A6 (CYP2A6)	OT52TWG3	CP2A6_HUMAN	Decreases Expression	[9]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[4]
Cytochrome P450 2C8 (CYP2C8)	OTHCWT42	CP2C8_HUMAN	Increases Expression	[4]
Cytochrome P450 2C9 (CYP2C9)	OTGLBN29	CP2C9_HUMAN	Increases Expression	[10]
Plasminogen activator inhibitor 1 (SERPINE1)	OTT0MPQ3	PAI1_HUMAN	Increases Expression	[11]
Retinol-binding protein 1 (RBP1)	OTRP1MFC	RET1_HUMAN	Decreases Expression	[12]
Peroxisome proliferator-activated receptor gamma (PPARG)	OTHMARHO	PPARG_HUMAN	Affects Binding	[8]
Stromal cell-derived factor 1 (CXCL12)	OT2QX5LL	SDF1_HUMAN	Decreases Expression	[12]
Carnitine O-palmitoyltransferase 1, liver isoform (CPT1A)	OTI862QH	CPT1A_HUMAN	Increases Expression	[12]
Peroxisome proliferator-activated receptor delta (PPARD)	OTI4WTOP	PPARD_HUMAN	Affects Binding	[8]
Perilipin-2 (PLIN2)	OTRXJ9UN	PLIN2_HUMAN	Increases Expression	[12]
Angiopoietin-related protein 4 (ANGPTL4)	OTQL5SPX	ANGL4_HUMAN	Increases Expression	[12]

Indication(s) of Sulfapyridine

Disease Entry	ICD 11	Status	REF
Dermatitis herpetiformis	EB44	Approved	[3]

Sulfapyridine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial Dihydropteroate synthetase (Bact folP)	TT4ILYC	DHPS_ECOLI	Inhibitor	[13]

Sulfapyridine Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
RNA cytidine acetyltransferase (hALP)	DEZV4AP	NAT10_HUMAN	Metabolism	[14]

Sulfapyridine Interacts with 6 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Growth-regulated alpha protein (CXCL1)	OT3WCTZV	GROA_HUMAN	Decreases Secretion	[15]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Decreases Secretion	[15]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Decreases Secretion	[15]
Metalloproteinase inhibitor 2 (TIMP2)	OT8S1RRP	TIMP2_HUMAN	Increases Expression	[16]
Arylamine N-acetyltransferase 2 (NAT2)	OTBPDQOY	ARY2_HUMAN	Increases Acetylation	[17]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Increases Transport	[17]

References

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• [2] Emerging antidyslipidemic drugs. Expert Opin Emerg Drugs. 2008 Jun;13(2):363-81.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] Comparative effects of fibrates on drug metabolizing enzymes in human hepatocytes. Pharm Res. 2005 Jan;22(1):71-8.
• [5] Complementary deoxyribonucleic acid cloning and expression of a human liver uridine diphosphate-glucuronosyltransferase glucuronidating carboxylic acid-containing drugs. J Pharmacol Exp Ther. 1993 Jan;264(1):475-9.
• [6] Gastrointestinally distributed UDP-glucuronosyltransferase 1A10, which metabolizes estrogens and nonsteroidal anti-inflammatory drugs, depends upon phosphorylation. J Biol Chem. 2004 Jul 2;279(27):28320-9. doi: 10.1074/jbc.M401396200. Epub 2004 Apr 26.
• [7] Carboxylic acid drug-induced DNA nicking in HEK293 cells expressing human UDP-glucuronosyltransferases: role of acyl glucuronide metabolites and glycation pathways. Chem Res Toxicol. 2007 Oct;20(10):1520-7. doi: 10.1021/tx700188x. Epub 2007 Sep 20.
• [8] Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB. Biochem Biophys Res Commun. 2002 Jan 11;290(1):131-9. doi: 10.1006/bbrc.2001.6141.
• [9] CYP2A5/CYP2A6 expression in mouse and human hepatocytes treated with various in vivo inducers. Drug Metab Dispos. 2000 Nov;28(11):1321-6.
• [10] Expression and induction potential of cytochromes P450 in human cryopreserved hepatocytes. Drug Metab Dispos. 2005 Jul;33(7):1004-16.
• [11] Effects of fibrate compounds on expression of plasminogen activator inhibitor-1 by cultured endothelial cells. Arterioscler Thromb Vasc Biol. 1999 Jun;19(6):1577-81. doi: 10.1161/01.atv.19.6.1577.
• [12] Decrease of hepatic stellate cells in rats with enhanced sensitivity to clofibrate-induced hepatocarcinogenesis. Cancer Sci. 2011 Apr;102(4):735-41. doi: 10.1111/j.1349-7006.2011.01856.x. Epub 2011 Feb 10.
• [13] A confirmatory method for the simultaneous extraction, separation, identification and quantification of Tetracycline, Sulphonamide, Trimethoprim an... J Chromatogr A. 2009 Nov 13;1216(46):8110-6.
• [14] Effects of NAT2 polymorphism on SASP pharmacokinetics in Chinese population. Clin Chim Acta. 2009 Sep;407(1-2):30-5.
• [15] The effect of sulfasalazine on rheumatoid arthritic synovial tissue chemokine production. Exp Mol Pathol. 2002 Oct;73(2):84-92. doi: 10.1006/exmp.2002.2460.
• [16] Effects of sulfasalazine and its metabolites on steady state messenger RNA concentrations for inflammatory cytokines, matrix metalloproteinases, and tissue inhibitors of metalloproteinase in rheumatoid synovial fibroblasts. J Rheumatol. 2000 Mar;27(3):653-60.
• [17] Pharmacogenetic characterization of sulfasalazine disposition based on NAT2 and ABCG2 (BCRP) gene polymorphisms in humans. Clin Pharmacol Ther. 2008 Jul;84(1):95-103.