Details of the Drug Combination

General Information of Drug Combination (ID: DCM1B1N)

Drug Combination Name
Ispinesib GSK461364
Indication
Disease Entry Status REF
Ewing sarcoma Investigative [1]
Component Drugs Ispinesib   DMP2BWX 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: 22.082
Bliss Independence Score: 19.345
Loewe Additivity Score: 3.985
LHighest Single Agent (HSA) Score: 8.189

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Ispinesib
Disease Entry ICD 11 Status REF
Head and neck cancer 2D42 Phase 2 [2]
Ovarian cancer 2C73 Phase 2 [2]
Renal cell carcinoma 2C90 Phase 2 [2]
Solid tumour/cancer 2A00-2F9Z Phase 2 [2]
Ispinesib Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Kinesin-like protein KIF11 (KIF11) TTTRP0H KIF11_HUMAN Inhibitor [4]
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Indication(s) of GSK461364
Disease Entry ICD 11 Status REF
Non-hodgkin lymphoma 2B33.5 Phase 1 [3]
Solid tumour/cancer 2A00-2F9Z Phase 1 [3]
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 [5]
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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 [6]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [6]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [6]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [6]
Serine-protein kinase ATM (ATM) OTQVOHLT ATM_HUMAN Increases Phosphorylation [6]
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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 ClinicalTrials.gov (NCT00095628) SB-715992 in Treating Patients With Recurrent or Metastatic Head and Neck Cancer. U.S. National Institutes of Health.
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: 5684).
4 Initial testing (stage 1) of the kinesin spindle protein inhibitor ispinesib by the pediatric preclinical testing program. Pediatr Blood Cancer. 2009 Dec 15;53(7):1255-63.
5 Polo-like kinase (PLK) inhibitors in preclinical and early clinical development in oncology. Oncologist. 2009 Jun;14(6):559-70.
6 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.