General Information of Drug Combination (ID: DCH4V9A)

Drug Combination Name
Pamidronate Efavirenz
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Pamidronate   DMB4AVP Efavirenz   DMC0GSJ
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: 5.22
Bliss Independence Score: 5.22
Loewe Additivity Score: 19.18
LHighest Single Agent (HSA) Score: 19.19

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Pamidronate
Disease Entry ICD 11 Status REF
Bone Paget disease N.A. Approved [2]
Hypercalcaemia 5B91.0 Approved [3]
Pamidronate Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Geranyltranstransferase (FDPS) TTIKWV4 FPPS_HUMAN Inhibitor [5]
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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 [6]
Osteocalcin (BGLAP) OTK1YLWQ OSTCN_HUMAN Increases Expression [6]
Alkaline phosphatase, tissue-nonspecific isozyme (ALPL) OTG7J4BP PPBT_HUMAN Increases Expression [6]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Decreases Expression [6]
Beta-2-microglobulin (B2M) OTDWN6NX B2MG_HUMAN Decreases Expression [6]
Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B) OTQ4W7MT TR11B_HUMAN Increases Expression [7]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Expression [8]
Collagen alpha-1(I) chain (COL1A1) OTI31178 CO1A1_HUMAN Decreases Expression [9]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [10]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [10]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Expression [11]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [11]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [11]
Transforming protein RhoA (RHOA) OT6YOJ9N RHOA_HUMAN Decreases Expression [11]
Ras-related protein Rap-1A (RAP1A) OT5RH6TI RAP1A_HUMAN Decreases Prenylation [12]
Rho-associated protein kinase 1 (ROCK1) OTSXYVW1 ROCK1_HUMAN Decreases Expression [11]
Fibroblast growth factor 23 (FGF23) OTZT523D FGF23_HUMAN Decreases Expression [13]
Bcl-2-interacting killer (BIK) OTTH1T3D BIK_HUMAN Increases Response To Substance [14]
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⏷ Show the Full List of 18 DOT(s)
Indication(s) of Efavirenz
Disease Entry ICD 11 Status REF
Human immunodeficiency virus infection 1C62 Approved [4]
Efavirenz Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human immunodeficiency virus Reverse transcriptase (HIV RT) TT84ETX POL_HV1B1 Modulator [15]
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Efavirenz Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [16]
Multidrug resistance-associated protein 3 (ABCC3) DTQ3ZHF MRP3_HUMAN Substrate [17]
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Efavirenz Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [18]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [19]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [20]
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Efavirenz Interacts with 32 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [21]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Decreases Activity [22]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Decreases Activity [22]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [23]
Dynamin-1-like protein (DNM1L) OTXK1Q1G DNM1L_HUMAN Affects Localization [24]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Increases Expression [25]
Dynamin-like 120 kDa protein, mitochondrial (OPA1) OTJGNWPW OPA1_HUMAN Increases Expression [24]
Mitofusin-2 (MFN2) OTPYN8A3 MFN2_HUMAN Increases Expression [24]
Thyroglobulin (TG) OT3ELHIJ THYG_HUMAN Increases Expression [26]
Albumin (ALB) OTVMM513 ALBU_HUMAN Affects Binding [27]
Plasminogen activator inhibitor 1 (SERPINE1) OTT0MPQ3 PAI1_HUMAN Increases Secretion [28]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Increases Secretion [28]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Increases Phosphorylation [25]
Lipoprotein lipase (LPL) OTTW0267 LIPL_HUMAN Decreases Expression [28]
Thyroid peroxidase (TPO) OTJJLL20 PERT_HUMAN Increases Expression [26]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Secretion [28]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Secretion [28]
Hepatocyte growth factor (HGF) OTGHUA23 HGF_HUMAN Increases Secretion [28]
Thyrotropin receptor (TSHR) OT0BC8LB TSHR_HUMAN Increases Expression [26]
Calnexin (CANX) OTYP1F6J CALX_HUMAN Affects Localization [24]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [24]
Lon protease homolog, mitochondrial (LONP1) OT665WYT LONM_HUMAN Increases Expression [24]
Sterol regulatory element-binding protein 1 (SREBF1) OTWBRPAI SRBP1_HUMAN Decreases Expression [28]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Decreases Expression [28]
Leptin (LEP) OT5Q7ODW LEP_HUMAN Decreases Expression [28]
Mitogen-activated protein kinase 8 (MAPK8) OTEREYS5 MK08_HUMAN Increases Phosphorylation [25]
CCAAT/enhancer-binding protein alpha (CEBPA) OTOM9OE4 CEBPA_HUMAN Decreases Expression [28]
Adiponectin (ADIPOQ) OTNX23LE ADIPO_HUMAN Decreases Expression [28]
Regulator of microtubule dynamics protein 3 (RMDN3) OTKO7AUM RMD3_HUMAN Increases Expression [24]
Mitogen-activated protein kinase kinase kinase 5 (MAP3K5) OTQR6ENW M3K5_HUMAN Increases Phosphorylation [25]
Eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3) OT0DZGY4 E2AK3_HUMAN Increases Expression [24]
Mitochondrial fission 1 protein (FIS1) OT2HL10J FIS1_HUMAN Increases Expression [24]
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⏷ Show the Full List of 32 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 Pamidronate 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: 7259).
4 Approved antiretroviral drugs. Antiretroviral Drugs. Company report of AVERT. 2009.
5 Detection of nonsterol isoprenoids by HPLC-MS/MS. Anal Biochem. 2008 Dec 1;383(1):18-24.
6 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.
7 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.
8 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.
9 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.
10 Bisphosphonates induce apoptosis in human breast cancer cell lines. Br J Cancer. 2000 Apr;82(8):1459-68. doi: 10.1054/bjoc.1999.1131.
11 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.
12 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.
13 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.
14 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.
15 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
16 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
17 Induction of multiple drug transporters by efavirenz. J Pharmacol Sci. 2009 Feb;109(2):242-50.
18 Induction of CYP3A4 by efavirenz in primary human hepatocytes: comparison with rifampin and phenobarbital. J Clin Pharmacol. 2004 Nov;44(11):1273-81.
19 CYP2B6 genotype-dependent inhibition of CYP1A2 and induction of CYP2A6 by the antiretroviral drug efavirenz in healthy volunteers. Clin Transl Sci. 2019 Nov;12(6):657-666.
20 Evaluation of CYP2B6 induction and prediction of clinical drug-drug interactions: considerations from the IQ consortium induction working group-an industry perspective. Drug Metab Dispos. 2016 Oct;44(10):1720-30.
21 Use of immortalized human hepatocytes to predict the magnitude of clinical drug-drug interactions caused by CYP3A4 induction. Drug Metab Dispos. 2006 Oct;34(10):1742-8.
22 Inhibition of human cytochrome P450 isoforms by nonnucleoside reverse transcriptase inhibitors. J Clin Pharmacol. 2001 Jan;41(1):85-91.
23 Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.
24 Lon protease: a novel mitochondrial matrix protein in the interconnection between drug-induced mitochondrial dysfunction and endoplasmic reticulum stress. Br J Pharmacol. 2017 Dec;174(23):4409-4429. doi: 10.1111/bph.14045. Epub 2017 Nov 7.
25 Efavirenz and 8-hydroxyefavirenz induce cell death via a JNK- and BimEL-dependent mechanism in primary human hepatocytes. Toxicol Appl Pharmacol. 2011 Dec 1;257(2):227-34. doi: 10.1016/j.taap.2011.09.008. Epub 2011 Sep 19.
26 Reverse transcriptase inhibitors down-regulate cell proliferation in vitro and in vivo and restore thyrotropin signaling and iodine uptake in human thyroid anaplastic carcinoma. J Clin Endocrinol Metab. 2005 Oct;90(10):5663-71. doi: 10.1210/jc.2005-0367. Epub 2005 Jul 19.
27 Binding of anti-HIV drugs to human serum albumin. IUBMB Life. 2004 Oct;56(10):609-14. doi: 10.1080/15216540400016286.
28 Effects of nevirapine and efavirenz on human adipocyte differentiation, gene expression, and release of adipokines and cytokines. Antiviral Res. 2011 Aug;91(2):112-9. doi: 10.1016/j.antiviral.2011.04.018. Epub 2011 May 17.