Details of the Drug

General Information of Drug (ID: DMUANF3)

Drug Name
MLN8054
Synonyms ZZL; MLN-8054
Indication
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 1 [1], [2]
Therapeutic Class
Anticancer Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 476.9
Topological Polar Surface Area (xlogp) 5.2
Rotatable Bond Count (rotbonds) 4
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 8
Chemical Identifiers
Formula
C25H15ClF2N4O2
IUPAC Name
4-[[9-chloro-7-(2,6-difluorophenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid
Canonical SMILES
C1C2=CN=C(N=C2C3=C(C=C(C=C3)Cl)C(=N1)C4=C(C=CC=C4F)F)NC5=CC=C(C=C5)C(=O)O
InChI
InChI=1S/C25H15ClF2N4O2/c26-15-6-9-17-18(10-15)23(21-19(27)2-1-3-20(21)28)29-11-14-12-30-25(32-22(14)17)31-16-7-4-13(5-8-16)24(33)34/h1-10,12H,11H2,(H,33,34)(H,30,31,32)
InChIKey
HHFBDROWDBDFBR-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
11712649
ChEBI ID
CHEBI:91366
CAS Number
869363-13-3
DrugBank ID
DB13061
TTD ID
D0A5MC
INTEDE ID
DR1810

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Aurora kinase A (AURKA) TTPS3C0 AURKA_HUMAN Inhibitor [3], [4], [5]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [6]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Substrate [6]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Solid tumour/cancer
ICD Disease Classification 2A00-2F9Z
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Aurora kinase A (AURKA) DTT AURKA 9.41E-46 -1.78 -2.05
Cytochrome P450 1A2 (CYP1A2) DME CYP1A2 7.09E-03 2.84E-02 1.20E-01
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 7.29E-03 -3.47E-02 -1.80E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

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2 ClinicalTrials.gov (NCT00652158) A Phase 1 Trial of Extended MLN8054 Dosing in Patients With Advanced Malignancies. U.S. National Institutes of Health.
3 A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
4 Clinical pipeline report, company report or official report of Takeda (2009).
5 MLN8054, a small-molecule inhibitor of Aurora A, causes spindle pole and chromosome congression defects leading to aneuploidy. Mol Cell Biol. 2007 Jun;27(12):4513-25.
6 MLN8054 and Alisertib (MLN8237): discovery of selective oral aurora A inhibitors. ACS Med Chem Lett. 2015 Apr 22;6(6):630-4.
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18 Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1). Drug Metab Dispos. 2014 Nov;42(11):1843-50.
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22 The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers. Sci Total Environ. 2007 Aug 1;381(1-3):38-46.
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26 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.
27 Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
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31 Clinical pipeline report, company report or official report of Cyclacel.