Details of the Drug Combination

General Information of Drug Combination (ID: DCIT9CE)

Drug Combination Name
Pazopanib HCl Everolimus
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Pazopanib HCl   DM6U9CQ Everolimus   DM8X2EH
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: 0.89
Bliss Independence Score: 0.89
Loewe Additivity Score: 6.51
LHighest Single Agent (HSA) Score: 6.57

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 [7]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [7]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [8]
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Indication(s) of Everolimus
Disease Entry ICD 11 Status REF
Advanced cancer 2A00-2F9Z Approved [3]
Advanced/metastatic breast cancer 2C60 Approved [4]
Brainstem neoplasm N.A. Approved [3]
Breast carcinoma N.A. Approved [3]
Graft-versus-host disease 4B24 Approved [3]
Intracranial meningioma N.A. Approved [3]
Leukemia N.A. Approved [3]
Lung cancer 2C25.0 Approved [3]
Mucosal melanoma N.A. Approved [3]
Multiple sclerosis 8A40 Approved [3]
Plasma cell myeloma 2A83.1 Approved [3]
Prostate cancer 2C82.0 Approved [3]
Renal cell carcinoma 2C90 Approved [5]
Salivary gland squamous cell carcinoma N.A. Approved [3]
Tuberous sclerosis LD2D.2 Approved [3]
Kidney cancer 2C90.0 Phase 3 [5]
Castration-resistant prostate carcinoma N.A. Investigative [3]
Colon cancer 2B90.Z Investigative [3]
Middle East Respiratory Syndrome (MERS) 1D64 Investigative [6]
Neuroblastoma 2D11.2 Investigative [3]
Pancreatic acinar cell carcinoma N.A. Investigative [3]
Polycystic kidney disease GB8Y Investigative [3]
Severe acute respiratory syndrome (SARS) 1D65 Investigative [6]
Everolimus Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Serine/threonine-protein kinase mTOR (mTOR) TTCJG29 MTOR_HUMAN Inhibitor [9]
HUMAN mammalian target of rapamycin (mTOR) TT7HQAF MTOR_HUMAN Inhibitor [6]
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Everolimus Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [10]
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Everolimus Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [11]
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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 Everolimus FDA Label
4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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: 5889).
6 Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
7 Bioavailability, metabolism and disposition of oral pazopanib in patients with advanced cancer. Xenobiotica. 2013 May;43(5):443-53.
8 Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
9 Mammalian target of rapamycin, its mode of action and clinical response in metastatic clear cell carcinoma. Gan To Kagaku Ryoho. 2009 Jul;36(7):1076-9.
10 Closer to the Site of Action: Everolimus Concentrations in Peripheral Blood Mononuclear Cells Correlate Well With Whole Blood Concentrations. Ther Drug Monit. 2015 Oct;37(5):675-80.
11 The evolving experience using everolimus in clinical transplantation. Transplant Proc. 2004 Mar;36(2 Suppl):495S-499S.