General Information of Drug Combination (ID: DCY0OL0)

Drug Combination Name
Cerivastatin Fibrates
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Cerivastatin   DMXCM7H 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: 4.01
Bliss Independence Score: 4.01
Loewe Additivity Score: 4.31
LHighest Single Agent (HSA) Score: 4.4

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Cerivastatin
Disease Entry ICD 11 Status REF
Hyperlipidaemia 5C80 Approved [2]
Multiple myeloma 2A83 Phase 1/2 [3]
Cerivastatin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
HMG-CoA reductase (HMGCR) TTPADOQ HMDH_HUMAN Inhibitor [3]
------------------------------------------------------------------------------------
Cerivastatin Interacts with 7 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [5]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [5]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [6]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [7]
Sodium/taurocholate cotransporting polypeptide (SLC10A1) DT56EKP NTCP_HUMAN Substrate [8]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [7]
Organic anion transporting polypeptide 2B1 (SLCO2B1) DTPFTEQ SO2B1_HUMAN Substrate [9]
------------------------------------------------------------------------------------
⏷ Show the Full List of 7 DTP(s)
Cerivastatin Interacts with 6 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [10]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [11]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [12]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [12]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [13]
UDP-glucuronosyltransferase 1A3 (UGT1A3) DEF2WXN UD13_HUMAN Metabolism [11]
------------------------------------------------------------------------------------
⏷ Show the Full List of 6 DME(s)
Cerivastatin Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Ryanodine receptor 2 (RYR2) OT0PF19E RYR2_HUMAN Increases ADR [14]
------------------------------------------------------------------------------------
Indication(s) of Fibrates
Disease Entry ICD 11 Status REF
Dyslipidemia 5C80-5C81 Investigative [4]
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 [4]
------------------------------------------------------------------------------------
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 [19]
Cytochrome P450 2A6 (CYP2A6) OT52TWG3 CP2A6_HUMAN Decreases Expression [20]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [15]
Cytochrome P450 2C8 (CYP2C8) OTHCWT42 CP2C8_HUMAN Increases Expression [15]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Increases Expression [21]
Plasminogen activator inhibitor 1 (SERPINE1) OTT0MPQ3 PAI1_HUMAN Increases Expression [22]
Retinol-binding protein 1 (RBP1) OTRP1MFC RET1_HUMAN Decreases Expression [23]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Affects Binding [19]
Stromal cell-derived factor 1 (CXCL12) OT2QX5LL SDF1_HUMAN Decreases Expression [23]
Carnitine O-palmitoyltransferase 1, liver isoform (CPT1A) OTI862QH CPT1A_HUMAN Increases Expression [23]
Peroxisome proliferator-activated receptor delta (PPARD) OTI4WTOP PPARD_HUMAN Affects Binding [19]
Perilipin-2 (PLIN2) OTRXJ9UN PLIN2_HUMAN Increases Expression [23]
Angiopoietin-related protein 4 (ANGPTL4) OTQL5SPX ANGL4_HUMAN Increases Expression [23]
------------------------------------------------------------------------------------
⏷ 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 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: 2950).
3 Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
4 Emerging antidyslipidemic drugs. Expert Opin Emerg Drugs. 2008 Jun;13(2):363-81.
5 Identification of the hepatic efflux transporters of organic anions using double-transfected Madin-Darby canine kidney II cells expressing human organic anion-transporting polypeptide 1B1 (OATP1B1)/multidrug resistance-associated protein 2, OATP1B1/multidrug resistance 1, and OATP1B1/breast cancer resistance protein. J Pharmacol Exp Ther. 2005 Sep;314(3):1059-67.
6 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
7 FDA Drug Development and Drug Interactions
8 Differential effect of genetic variants of Na(+)-taurocholate co-transporting polypeptide (NTCP) and organic anion-transporting polypeptide 1B1 (OATP1B1) on the uptake of HMG-CoA reductase inhibitors. Xenobiotica. 2011 Jan;41(1):24-34.
9 pH-sensitive interaction of HMG-CoA reductase inhibitors (statins) with organic anion transporting polypeptide 2B1. Mol Pharm. 2011 Aug 1;8(4):1303-13.
10 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
11 Cerivastatin, genetic variants, and the risk of rhabdomyolysis. Pharmacogenet Genomics. 2011 May;21(5):280-8.
12 Drug Interactions Flockhart Table
13 Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
14 Cerivastatin, genetic variants, and the risk of rhabdomyolysis. Pharmacogenet Genomics. 2011 May;21(5):280-8.
15 Comparative effects of fibrates on drug metabolizing enzymes in human hepatocytes. Pharm Res. 2005 Jan;22(1):71-8.
16 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.
17 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.
18 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.
19 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.
20 CYP2A5/CYP2A6 expression in mouse and human hepatocytes treated with various in vivo inducers. Drug Metab Dispos. 2000 Nov;28(11):1321-6.
21 Expression and induction potential of cytochromes P450 in human cryopreserved hepatocytes. Drug Metab Dispos. 2005 Jul;33(7):1004-16.
22 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.
23 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.