Details of the Drug Combination

General Information of Drug Combination (ID: DC819RJ)

Drug Combination Name
MLN8237 BMS-754807
Indication
Disease Entry Status REF
Diffuse intrinsic pontine glioma Investigative [1]
Component Drugs MLN8237   DMO8PT9 BMS-754807   DMPK32V
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: SU-DIPG-XIII
Zero Interaction Potency (ZIP) Score: 7.31
Bliss Independence Score: 15.265
Loewe Additivity Score: 13.928
LHighest Single Agent (HSA) Score: 14.016

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of MLN8237
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 3 [2]
Small-cell lung cancer 2C25.Y Phase 2 [3]
MLN8237 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Aurora kinase A (AURKA) TTPS3C0 AURKA_HUMAN Inhibitor [4]
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MLN8237 Interacts with 11 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
N-myc proto-oncogene protein (MYCN) OTWD33K1 MYCN_HUMAN Decreases Expression [5]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Affects Activity [6]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [7]
Cytochrome P450 2C8 (CYP2C8) OTHCWT42 CP2C8_HUMAN Affects Activity [6]
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Affects Activity [6]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Affects Activity [6]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Affects Activity [6]
Multidrug resistance-associated protein 1 (ABCC1) OTGUN89S MRP1_HUMAN Decreases Activity [6]
Aurora kinase B (AURKB) OTIY4VHU AURKB_HUMAN Decreases Activity [7]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Affects Activity [6]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Transport [6]
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⏷ Show the Full List of 11 DOT(s)
BMS-754807 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
RAC-alpha serine/threonine-protein kinase (AKT1) TTWTSCV AKT1_HUMAN Inhibitor [8]
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BMS-754807 Interacts with 6 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Phosphorylation [9]
Insulin-like growth factor 1 receptor (IGF1R) OTXJIF13 IGF1R_HUMAN Decreases Phosphorylation [9]
Ribosomal protein S6 kinase beta-1 (RPS6KB1) OTAELNGX KS6B1_HUMAN Decreases Phosphorylation [9]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Increases Response To Substance [9]
Cyclin-dependent kinase inhibitor 2A (CDKN2A) OTN0ZWAE CDN2A_HUMAN Decreases Response To Substance [9]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Response To Substance [9]
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⏷ Show the Full List of 6 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: 7790).
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 Effect of Aurora A kinase inhibitor MLN8237 combined with rituximab on antitumor activity in preclinical B-cell non-Hodgkin's lymphoma models. Journal of Clinical Oncology, 2009:8553.
5 A Cre-conditional MYCN-driven neuroblastoma mouse model as an improved tool for preclinical studies. Oncogene. 2015 Jun;34(26):3357-68. doi: 10.1038/onc.2014.269. Epub 2014 Sep 1.
6 Alisertib shows negligible potential for perpetrating pharmacokinetic drug-drug interactions on ABCB1, ABCG2 and cytochromes P450, but acts as dual-activity resistance modulator through the inhibition of ABCC1 transporter. Toxicol Appl Pharmacol. 2022 Jan 1;434:115823. doi: 10.1016/j.taap.2021.115823. Epub 2021 Dec 9.
7 Aurora inhibitor MLN8237 in combination with docetaxel enhances apoptosis and anti-tumor activity in mantle cell lymphoma. Biochem Pharmacol. 2011 Apr 1;81(7):881-90. doi: 10.1016/j.bcp.2011.01.017. Epub 2011 Feb 1.
8 Discovery of a 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine inhibitor (BMS-754807) of insulin-like growth factor receptor (IGF-1R) kinase in cli... J Med Chem. 2009 Dec 10;52(23):7360-3.
9 CDK4/6 and IGF1 receptor inhibitors synergize to suppress the growth of p16INK4A-deficient pancreatic cancers. Cancer Res. 2014 Jul 15;74(14):3947-58. doi: 10.1158/0008-5472.CAN-13-2923. Epub 2014 Jul 1.