General Information of Drug Combination (ID: DCX9ERF)

Drug Combination Name
Cerivastatin Pamidronate
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Cerivastatin   DMXCM7H Pamidronate   DMB4AVP
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: 4.8
Bliss Independence Score: 4.8
Loewe Additivity Score: 5.14
LHighest Single Agent (HSA) Score: 5.24

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 [6]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [6]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [7]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [8]
Sodium/taurocholate cotransporting polypeptide (SLC10A1) DT56EKP NTCP_HUMAN Substrate [9]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [8]
Organic anion transporting polypeptide 2B1 (SLCO2B1) DTPFTEQ SO2B1_HUMAN Substrate [10]
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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 [11]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [12]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [13]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Metabolism [13]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [14]
UDP-glucuronosyltransferase 1A3 (UGT1A3) DEF2WXN UD13_HUMAN Metabolism [12]
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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 [15]
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Indication(s) of Pamidronate
Disease Entry ICD 11 Status REF
Bone Paget disease N.A. Approved [4]
Hypercalcaemia 5B91.0 Approved [5]
Pamidronate Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Geranyltranstransferase (FDPS) TTIKWV4 FPPS_HUMAN Inhibitor [16]
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Pamidronate Interacts with 18 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
C-reactive protein (CRP) OT0RFT8F CRP_HUMAN Decreases Expression [17]
Osteocalcin (BGLAP) OTK1YLWQ OSTCN_HUMAN Increases Expression [17]
Alkaline phosphatase, tissue-nonspecific isozyme (ALPL) OTG7J4BP PPBT_HUMAN Increases Expression [17]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Decreases Expression [17]
Beta-2-microglobulin (B2M) OTDWN6NX B2MG_HUMAN Decreases Expression [17]
Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B) OTQ4W7MT TR11B_HUMAN Increases Expression [18]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Expression [19]
Collagen alpha-1(I) chain (COL1A1) OTI31178 CO1A1_HUMAN Decreases Expression [20]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [21]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [21]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Expression [22]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [22]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [22]
Transforming protein RhoA (RHOA) OT6YOJ9N RHOA_HUMAN Decreases Expression [22]
Ras-related protein Rap-1A (RAP1A) OT5RH6TI RAP1A_HUMAN Decreases Prenylation [23]
Rho-associated protein kinase 1 (ROCK1) OTSXYVW1 ROCK1_HUMAN Decreases Expression [22]
Fibroblast growth factor 23 (FGF23) OTZT523D FGF23_HUMAN Decreases Expression [24]
Bcl-2-interacting killer (BIK) OTTH1T3D BIK_HUMAN Increases Response To Substance [25]
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⏷ Show the Full List of 18 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 Pamidronate FDA Label
5 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: 7259).
6 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.
7 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.
8 FDA Drug Development and Drug Interactions
9 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.
10 pH-sensitive interaction of HMG-CoA reductase inhibitors (statins) with organic anion transporting polypeptide 2B1. Mol Pharm. 2011 Aug 1;8(4):1303-13.
11 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.
12 Cerivastatin, genetic variants, and the risk of rhabdomyolysis. Pharmacogenet Genomics. 2011 May;21(5):280-8.
13 Drug Interactions Flockhart Table
14 Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
15 Cerivastatin, genetic variants, and the risk of rhabdomyolysis. Pharmacogenet Genomics. 2011 May;21(5):280-8.
16 Detection of nonsterol isoprenoids by HPLC-MS/MS. Anal Biochem. 2008 Dec 1;383(1):18-24.
17 Pamidronate increases markers of bone formation in patients with multiple myeloma in plateau phase under interferon-alpha treatment. Calcif Tissue Int. 2001 May;68(5):285-90.
18 Bisphosphonates pamidronate and zoledronic acid stimulate osteoprotegerin production by primary human osteoblasts. Biochem Biophys Res Commun. 2002 Mar 1;291(3):680-6. doi: 10.1006/bbrc.2002.6510.
19 An in vitro and in vivo study of cytokines in the acute-phase response associated with bisphosphonates. Calcif Tissue Int. 1997 Nov;61(5):386-92. doi: 10.1007/s002239900353.
20 Expression profile and synthesis of different collagen types I, II, III, and V of human gingival fibroblasts, osteoblasts, and SaOS-2 cells after bisphosphonate treatment. Clin Oral Investig. 2010 Feb;14(1):51-8. doi: 10.1007/s00784-009-0312-2. Epub 2009 Jul 14.
21 Bisphosphonates induce apoptosis in human breast cancer cell lines. Br J Cancer. 2000 Apr;82(8):1459-68. doi: 10.1054/bjoc.1999.1131.
22 Pamidronate induced anti-proliferative, apoptotic, and anti-migratory effects in hepatocellular carcinoma. J Hepatol. 2006 Jan;44(1):142-50. doi: 10.1016/j.jhep.2005.09.022. Epub 2005 Nov 9.
23 Nitrogen-containing bisphosphonates induce apoptosis of Caco-2 cells in vitro by inhibiting the mevalonate pathway: a model of bisphosphonate-induced gastrointestinal toxicity. Bone. 2001 Oct;29(4):336-43. doi: 10.1016/s8756-3282(01)00589-0.
24 The role of fibroblast growth factor 23 for hypophosphatemia and abnormal regulation of vitamin D metabolism in patients with McCune-Albright syndrome. J Bone Miner Metab. 2005;23(3):231-7. doi: 10.1007/s00774-004-0589-9.
25 Caspase-independent induction of apoptosis in human melanoma cells by the proapoptotic Bcl-2-related protein Nbk / Bik. Oncogene. 2005 Nov 10;24(49):7369-80. doi: 10.1038/sj.onc.1208890.