Details of the Drug Combination

General Information of Drug Combination (ID: DC2ALAO)

Drug Combination Name
Pazopanib HCl Diazoxide
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Pazopanib HCl   DM6U9CQ 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: 2.07
Bliss Independence Score: 2.07
Loewe Additivity Score: 2.68
LHighest Single Agent (HSA) Score: 2.68

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Pazopanib HCl
Disease Entry ICD 11 Status REF
Renal cell carcinoma 2C90 Approved [2]
Pazopanib HCl Interacts with 3 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Platelet-derived growth factor receptor (PDGFR) TTI2WET NOUNIPROTAC Inhibitor [2]
Tyrosine-protein kinase Kit (KIT) TTX41N9 KIT_HUMAN Inhibitor [2]
Vascular endothelial growth factor receptor 2 (KDR) TTUTJGQ VGFR2_HUMAN Inhibitor [2]
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Pazopanib HCl Interacts with 3 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [5]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [5]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [6]
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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 [7]
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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 [8]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Decreases Secretion [8]
Nuclear factor NF-kappa-B p105 subunit (NFKB1) OTNRRD8I NFKB1_HUMAN Increases Activity [9]
Interleukin-10 (IL10) OTIRFRXC IL10_HUMAN Decreases Secretion [8]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [10]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Decreases Expression [10]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Increases Expression [9]
ATP-sensitive inward rectifier potassium channel 11 (KCNJ11) OTPUUELV KCJ11_HUMAN Decreases Expression [11]
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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 Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
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 Bioavailability, metabolism and disposition of oral pazopanib in patients with advanced cancer. Xenobiotica. 2013 May;43(5):443-53.
6 Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
7 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
8 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.
9 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.
10 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.
11 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.