General Information of Drug Combination (ID: DCHJ5YQ)

Drug Combination Name
Sitagliptin Fibrates
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Sitagliptin   DMGDKXN Fibrates   DMFNTMY
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 1.4
Bliss Independence Score: 1.4
Loewe Additivity Score: 14.21
LHighest Single Agent (HSA) Score: 14.22

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Sitagliptin
Disease Entry ICD 11 Status REF
Cystic fibrosis CA25 Approved [2]
Non-insulin dependent diabetes 5A11 Approved [2]
Renal hypoplasia N.A. Approved [2]
Type-2 diabetes 5A11 Approved [3]
Peripheral arterial disease BD4Z Phase 1/2 [4]
Sitagliptin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Dipeptidyl peptidase 4 (DPP-4) TTDIGC1 DPP4_HUMAN Inhibitor [6]
------------------------------------------------------------------------------------
Sitagliptin Interacts with 3 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [7]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [8]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [9]
------------------------------------------------------------------------------------
Sitagliptin Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [10]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [10]
------------------------------------------------------------------------------------
Indication(s) of Fibrates
Disease Entry ICD 11 Status REF
Dyslipidemia 5C80-5C81 Investigative [5]
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 [5]
------------------------------------------------------------------------------------
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 [15]
Cytochrome P450 2A6 (CYP2A6) OT52TWG3 CP2A6_HUMAN Decreases Expression [16]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [11]
Cytochrome P450 2C8 (CYP2C8) OTHCWT42 CP2C8_HUMAN Increases Expression [11]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Increases Expression [17]
Plasminogen activator inhibitor 1 (SERPINE1) OTT0MPQ3 PAI1_HUMAN Increases Expression [18]
Retinol-binding protein 1 (RBP1) OTRP1MFC RET1_HUMAN Decreases Expression [19]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Affects Binding [15]
Stromal cell-derived factor 1 (CXCL12) OT2QX5LL SDF1_HUMAN Decreases Expression [19]
Carnitine O-palmitoyltransferase 1, liver isoform (CPT1A) OTI862QH CPT1A_HUMAN Increases Expression [19]
Peroxisome proliferator-activated receptor delta (PPARD) OTI4WTOP PPARD_HUMAN Affects Binding [15]
Perilipin-2 (PLIN2) OTRXJ9UN PLIN2_HUMAN Increases Expression [19]
Angiopoietin-related protein 4 (ANGPTL4) OTQL5SPX ANGL4_HUMAN Increases Expression [19]
------------------------------------------------------------------------------------
⏷ Show the Full List of 13 DOT(s)

References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
2 Sitagliptin FDA Label
3 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: 6286).
4 ClinicalTrials.gov (NCT01619332) Clinical Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LEZ763. U.S. National Institutes of Health.
5 Emerging antidyslipidemic drugs. Expert Opin Emerg Drugs. 2008 Jun;13(2):363-81.
6 Novel therapeutics for type 2 diabetes: incretin hormone mimetics (glucagon-like peptide-1 receptor agonists) and dipeptidyl peptidase-4 inhibitors. Pharmacol Ther. 2009 Oct;124(1):113-38.
7 Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
8 265 effect of dietary cholesterol on gallbladder bile lithogenicity and gene expression in the enterohepatic axis of non-obese gallstone and control women. Journal of Hepatology, 2009, 50(09):S105-S106.
9 Transport of the dipeptidyl peptidase-4 inhibitor sitagliptin by human organic anion transporter 3, organic anion transporting polypeptide 4C1, and multidrug resistance P-glycoprotein. J Pharmacol Exp Ther. 2007 May;321(2):673-83.
10 Pharmacokinetics of dipeptidylpeptidase-4 inhibitors. Diabetes Obes Metab. 2010 Aug;12(8):648-58.
11 Comparative effects of fibrates on drug metabolizing enzymes in human hepatocytes. Pharm Res. 2005 Jan;22(1):71-8.
12 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.
13 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.
14 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.
15 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.
16 CYP2A5/CYP2A6 expression in mouse and human hepatocytes treated with various in vivo inducers. Drug Metab Dispos. 2000 Nov;28(11):1321-6.
17 Expression and induction potential of cytochromes P450 in human cryopreserved hepatocytes. Drug Metab Dispos. 2005 Jul;33(7):1004-16.
18 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.
19 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.