Details of the Drug Combination

General Information of Drug Combination (ID: DCWFWE1)

Drug Combination Name
MLN8237 SNS-032
Indication
Disease Entry Status REF
Diffuse intrinsic pontine glioma Investigative [1]
Component Drugs MLN8237   DMO8PT9 SNS-032   DMEITAS
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: 20.269
Bliss Independence Score: 30.16
Loewe Additivity Score: 4.339
LHighest Single Agent (HSA) Score: 7.354

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 [5]
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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 [6]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Affects Activity [7]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [8]
Cytochrome P450 2C8 (CYP2C8) OTHCWT42 CP2C8_HUMAN Affects Activity [7]
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Affects Activity [7]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Affects Activity [7]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Affects Activity [7]
Multidrug resistance-associated protein 1 (ABCC1) OTGUN89S MRP1_HUMAN Decreases Activity [7]
Aurora kinase B (AURKB) OTIY4VHU AURKB_HUMAN Decreases Activity [8]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Affects Activity [7]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Transport [7]
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⏷ Show the Full List of 11 DOT(s)
Indication(s) of SNS-032
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 1 [4]
SNS-032 Interacts with 3 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Cyclin-dependent kinase 9 (CDK9) TT1LVF2 CDK9_HUMAN Inhibitor [9]
Cyclin-dependent kinase 7 (CDK7) TTQYF7G CDK7_HUMAN Inhibitor [9]
Cyclin-dependent kinase 2 (CDK2) TT7HF4W CDK2_HUMAN Inhibitor [9]
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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 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 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: 5670).
5 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.
6 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.
7 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.
8 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.
9 Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. Blood. 2009 May 7;113(19):4637-45.