Details of the Drug Combination

General Information of Drug Combination (ID: DC71PVO)

Drug Combination Name
Procarbazine Diazoxide
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Procarbazine   DMIK367 Diazoxide   DML1538
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: 0.38
Bliss Independence Score: 0.38
Loewe Additivity Score: 1.01
LHighest Single Agent (HSA) Score: 1.01

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Procarbazine
Disease Entry ICD 11 Status REF
Hodgkin lymphoma 2B30 Approved [2]
Procarbazine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC . [5]
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Procarbazine Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [6]
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [6]
Cytochrome P450 1B1 (CYP1B1) DE9QHP6 CP1B1_HUMAN Metabolism [7]
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Indication(s) of Diazoxide
Disease Entry ICD 11 Status REF
Congenital hyperinsulinism 5A4Y Approved [3]
Hyperinsulinemia 5A4Y Approved [3]
Hypertension BA00-BA04 Approved [4]
Hypertensive emergency BA03 Approved [3]
Insulinoma 2C10.1 Approved [3]
Malignant essential hypertension BA00 Approved [3]
Diazoxide Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Potassium channel unspecific (KC) TT1VOHK NOUNIPROTAC Modulator [8]
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Diazoxide Interacts with 8 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Decreases Secretion [9]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Decreases Secretion [9]
Nuclear factor NF-kappa-B p105 subunit (NFKB1) OTNRRD8I NFKB1_HUMAN Increases Activity [10]
Interleukin-10 (IL10) OTIRFRXC IL10_HUMAN Decreases Secretion [9]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [11]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Decreases Expression [11]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Increases Expression [10]
ATP-sensitive inward rectifier potassium channel 11 (KCNJ11) OTPUUELV KCJ11_HUMAN Decreases Expression [12]
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⏷ Show the Full List of 8 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: 7278).
3 Diazoxide FDA Label
4 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: 2409).
5 Brca2/Xrcc2 dependent HR, but not NHEJ, is required for protection against O(6)-methylguanine triggered apoptosis, DSBs and chromosomal aberrations... DNA Repair (Amst). 2009 Jan 1;8(1):72-86.
6 In vitro and in vivo evidence for the formation of methyl radical from procarbazine: a spin-trapping study. Carcinogenesis. 1992 May;13(5):799-805.
7 Tumour cytochrome P450 and drug activation. Curr Pharm Des. 2002;8(15):1335-47.
8 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
9 Antihypertensive drugs clonidine, diazoxide, hydralazine and furosemide regulate the production of cytokines by placentas and peripheral blood mononuclear cells in normal pregnancy. J Hypertens. 2006 May;24(5):915-22. doi: 10.1097/01.hjh.0000222762.84605.03.
10 Diazoxide-mediated preconditioning against apoptosis involves activation of cAMP-response element-binding protein (CREB) and NFkappaB. J Biol Chem. 2004 Nov 5;279(45):46748-54. doi: 10.1074/jbc.M406217200. Epub 2004 Aug 23.
11 Diazoxide-mediated growth inhibition in human lung cancer cells via downregulation of beta-catenin-mediated cyclin D1 transcription. Lung. 2009 Jan-Feb;187(1):61-7. doi: 10.1007/s00408-008-9127-1. Epub 2008 Dec 4.
12 Combined contributions of over-secreted glucagon-like peptide 1 and suppressed insulin secretion to hyperglycemia induced by gatifloxacin in rats. Toxicol Appl Pharmacol. 2013 Feb 1;266(3):375-84. doi: 10.1016/j.taap.2012.11.015. Epub 2012 Nov 28.