Details of the Drug Combination

General Information of Drug Combination (ID: DCQD4LB)

Drug Combination Name
Lenvatinib GSK461364
Indication
Disease Entry Status REF
Ewing sarcoma Investigative [1]
Component Drugs Lenvatinib   DMB1IU4 GSK461364   DM0P729
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: TC-71
Zero Interaction Potency (ZIP) Score: 44.973
Bliss Independence Score: 46.824
Loewe Additivity Score: 10.737
LHighest Single Agent (HSA) Score: 14.616

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Lenvatinib
Disease Entry ICD 11 Status REF
Thyroid cancer 2D10 Approved [2]
Thyroid gland follicular carcinoma N.A. Approved [3]
Thyroid gland papillary carcinoma N.A. Approved [3]
Hepatocellular carcinoma 2C12.02 Phase 3 [4]
Renal cell carcinoma 2C90 Phase 3 [5]
Melanoma 2C30 Phase 2 [4]
Solid tumour/cancer 2A00-2F9Z Phase 1/2 [5]
Ovarian cancer 2C73 Phase 1 [6]
Non-small-cell lung cancer 2C25.Y Application submitted [5]
Lenvatinib Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Vascular endothelial growth factor receptor 2 (KDR) TTUTJGQ VGFR2_HUMAN Inhibitor [6]
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Lenvatinib Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [8]
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Indication(s) of GSK461364
Disease Entry ICD 11 Status REF
Non-hodgkin lymphoma 2B33.5 Phase 1 [7]
Solid tumour/cancer 2A00-2F9Z Phase 1 [7]
GSK461364 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Polo-like kinase 1 (PLK1) TTIYVQP PLK1_HUMAN Inhibitor [9]
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GSK461364 Interacts with 5 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [10]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [10]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [10]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [10]
Serine-protein kinase ATM (ATM) OTQVOHLT ATM_HUMAN Increases Phosphorylation [10]
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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 FDA Approved Drug Products from FDA Official Website. 2018. Application Number: (ANDA) 208627.
3 Lenvatinib FDA Label
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
6 Emerging drugs for ovarian cancer. Expert Opin Emerg Drugs. 2008 Sep;13(3):523-36.
7 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: 5684).
8 Influence of CYP3A4/5 and ABC transporter polymorphisms on lenvatinib plasma trough concentrations in Japanese patients with thyroid cancer. Sci Rep. 2019 Apr 1;9(1):5404.
9 Polo-like kinase (PLK) inhibitors in preclinical and early clinical development in oncology. Oncologist. 2009 Jun;14(6):559-70.
10 A specific inhibitor of polo-like kinase 1, GSK461364A, suppresses proliferation of Raji Burkitt's lymphoma cells through mediating cell cycle arrest, DNA damage, and apoptosis. Chem Biol Interact. 2020 Dec 1;332:109288. doi: 10.1016/j.cbi.2020.109288. Epub 2020 Oct 17.