Details of the Drug Combination

General Information of Drug Combination (ID: DC3L73P)

Drug Combination Name
MLN2480 MLN8237
Indication
Disease Entry Status REF
Advanced Nonhematologic Malignancies Phase 1 [1]
Component Drugs MLN2480   DMBR8NF MLN8237   DMO8PT9
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of MLN2480
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 2 [2]
Melanoma 2C30 Phase 1 [3]
MLN2480 Interacts with 3 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Serine/threonine-protein kinase Raf (RAF) TTQ9K3Y ARAF_HUMAN; BRAF_HUMAN; RAF1_HUMAN Inhibitor [2]
Raf messenger RNA (Raf mRNA) TTAN5W2 RAF1_HUMAN Inhibitor [6]
B-Raf messenger RNA (BRAF mRNA) TT0EOB8 BRAF_HUMAN Inhibitor [7]
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Indication(s) of MLN8237
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 3 [4]
Small-cell lung cancer 2C25.Y Phase 2 [5]
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 [8]
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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 [9]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Affects Activity [10]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [11]
Cytochrome P450 2C8 (CYP2C8) OTHCWT42 CP2C8_HUMAN Affects Activity [10]
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Affects Activity [10]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Affects Activity [10]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Affects Activity [10]
Multidrug resistance-associated protein 1 (ABCC1) OTGUN89S MRP1_HUMAN Decreases Activity [10]
Aurora kinase B (AURKB) OTIY4VHU AURKB_HUMAN Decreases Activity [11]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Affects Activity [10]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Transport [10]
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⏷ Show the Full List of 11 DOT(s)

References

1 ClinicalTrials.gov (NCT02327169) A Study MLN2480 in Combination With MLN0128 or Alisertib, or Paclitaxel, or Cetuximab, or Irinotecan in Adult Participants With Advanced Nonhematologic Malignancies
2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3 ClinicalTrials.gov (NCT01425008) Study of MLN2480 in Patients With Relapsed or Refractory Solid Tumors Followed by a Dose Expansion in Patients With Metastatic Melanoma. U.S. National Institutes of Health.
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: 7790).
5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
6 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. (Target id: 2184).
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. (Target id: 1943).
8 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.
9 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.
10 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.
11 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.