General Information of Drug Combination (ID: DC5UJ30)

Drug Combination Name
Cerivastatin Emetine
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Cerivastatin   DMXCM7H Emetine   DMCT2YF
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: 1.2
Bliss Independence Score: 1.2
Loewe Additivity Score: 3.29
LHighest Single Agent (HSA) Score: 3.38

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]
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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]
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⏷ 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]
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⏷ 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]
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Indication(s) of Emetine
Disease Entry ICD 11 Status REF
Hepatitis virus infection 1E50-1E51 Approved [4]
Emetine Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [16]
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Emetine Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [17]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [17]
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Emetine Interacts with 15 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) OT9QIHEQ RECK_HUMAN Decreases Expression [18]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Decreases Activity [19]
N-myc proto-oncogene protein (MYCN) OTWD33K1 MYCN_HUMAN Increases Degradation [20]
72 kDa type IV collagenase (MMP2) OT5NIWA2 MMP2_HUMAN Decreases Expression [18]
Interleukin-6 receptor subunit alpha (IL6R) OTCQL07Z IL6RA_HUMAN Decreases Expression [15]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [21]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Decreases Expression [15]
C-C motif chemokine 3 (CCL3) OTW2H3ND CCL3_HUMAN Decreases Expression [15]
Microtubule-associated protein tau (MAPT) OTMTP2Z7 TAU_HUMAN Decreases Expression [22]
C-C motif chemokine 4 (CCL4) OT6B8P25 CCL4_HUMAN Decreases Expression [15]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Decreases Expression [15]
C-C motif chemokine 5 (CCL5) OTSCA5CK CCL5_HUMAN Decreases Expression [15]
Matrix metalloproteinase-9 (MMP9) OTB2QDAV MMP9_HUMAN Decreases Expression [18]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [18]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [18]
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⏷ Show the Full List of 15 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 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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 Cell-based and cytokine-directed chemical screen to identify potential anti-multiple myeloma agents. Leuk Res. 2010 Jul;34(7):917-24. doi: 10.1016/j.leukres.2009.12.002. Epub 2010 Feb 8.
16 Potential role of drug transporters in the pathogenesis of medically intractable epilepsy. Epilepsia. 2005 Feb;46(2):224-35.
17 Metabolism of ipecac alkaloids cephaeline and emetine by human hepatic microsomal cytochrome P450s, and their inhibitory effects on P450 enzyme activities. Biol Pharm Bull. 2001 Jun;24(6):678-82.
18 Emetine inhibits migration and invasion of human non-small-cell lung cancer cells via regulation of ERK and p38 signaling pathways. Chem Biol Interact. 2015 Dec 5;242:25-33. doi: 10.1016/j.cbi.2015.08.014. Epub 2015 Aug 30.
19 Identification and Profiling of Environmental Chemicals That Inhibit the TGF/SMAD Signaling Pathway. Chem Res Toxicol. 2019 Dec 16;32(12):2433-2444. doi: 10.1021/acs.chemrestox.9b00228. Epub 2019 Nov 11.
20 IGF2BP1 induces neuroblastoma via a druggable feedforward loop with MYCN promoting 17q oncogene expression. Mol Cancer. 2023 May 29;22(1):88. doi: 10.1186/s12943-023-01792-0.
21 Apoptosis induces Bcl-XS and cleaved Bcl-XL in chronic lymphocytic leukaemia. Biochem Biophys Res Commun. 2011 Feb 18;405(3):480-5. doi: 10.1016/j.bbrc.2011.01.057. Epub 2011 Jan 20.
22 Pharmacologic reductions of total tau levels; implications for the role of microtubule dynamics in regulating tau expression. Mol Neurodegener. 2006 Jul 26;1:6. doi: 10.1186/1750-1326-1-6.