Details
Stereochemistry | ACHIRAL |
Molecular Formula | C27H20ClFN4O4 |
Molecular Weight | 518.924 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CC(NC2=NC=C3CN=C(C4=CC(Cl)=CC=C4C3=N2)C5=C(OC)C=CC=C5F)=CC=C1C(O)=O
InChI
InChIKey=ZLHFILGSQDJULK-UHFFFAOYSA-N
InChI=1S/C27H20ClFN4O4/c1-36-21-5-3-4-20(29)23(21)25-19-10-15(28)6-8-17(19)24-14(12-30-25)13-31-27(33-24)32-16-7-9-18(26(34)35)22(11-16)37-2/h3-11,13H,12H2,1-2H3,(H,34,35)(H,31,32,33)
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/22016509Curator's Comment: Description was created based on several sources, including
https://www.takeda.com/news/2012/20120306_3946.html
http://adisinsight.springer.com/drugs/800025209
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22016509
Curator's Comment: Description was created based on several sources, including
https://www.takeda.com/news/2012/20120306_3946.html
http://adisinsight.springer.com/drugs/800025209
Alisertib (MLN8237) is an orally available selective aurora A kinase inhibitor developed by Takeda. Alisertib inhibited AAK over ABK with a selectivity of more than 200-fold in cells and produced a dose-dependent decrease in bipolar and aligned chromosomes in the HCT-116 xenograft model, a phenotype consistent with AAK inhibition. Alisertib inhibited proliferation of human tumor cell lines in vitro and produced tumor growth inhibition in solid tumor xenograft models and regressions in in vivo lymphoma models. It is currently in phase II clinical trials for acute myeloid leukaemia; B cell lymphoma; brain cancer; mesothelioma; prostate cancer; small cell lung cancer.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25533335
Curator's Comment: Alisertib (MLN8237) achieved blood-brain barrier penetration
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL4722 |
1.2 nM [IC50] | ||
Target ID: CHEMBL1075413 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25074669 |
76.7 nM [IC50] | ||
Target ID: CHEMBL396 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22016509 |
16.0 nM [IC50] | ||
Target ID: CHEMBL390 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22016509 |
54.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT01799278
50 mg twice daily for 7 days repeated every 21 days,
administered on an empty stomach with the patient remaining nothing by mouth (NPO), except for water and prescribed medications, for 2 hours before and 1 hour after each dose, oral dose of Alisertib (MLN8237) should be taken with 8 ounces (1 cup, 240 mL) of water.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20382844
Alisertib (MLN8237) (0.5 uM) treatment inhibits the phosphorylation of Aurora A in human MM1.S and OPM1 cells, without affecting the Aurora B mediated histone H3 phosphorylation. Alisertib (MLN8237) (0.5 uM) induces 2- to 6-fold increase in G2/M phase in primary MM cells and cell lines, as well as significant apoptosis and senescence, involving the up-regulation of p53, p21 and p27, as well as PARP, caspase 3, and caspase 9 cleavage.
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C129825
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NCI_THESAURUS |
C62556
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FDA ORPHAN DRUG |
400313
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EU-Orphan Drug |
EU/3/12/1074
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FDA ORPHAN DRUG |
369112
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SUB128442
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Alisertib
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T66ES73M18
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100000153914
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C71717
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DTXSID30145539
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DB05220
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C550258
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CHEMBL483158
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24771867
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9331
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1028486-01-2
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XX-123
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ACTIVE MOIETY
METABOLITE (PARENT)
METABOLITE (PARENT)
SALT/SOLVATE (PARENT)
SALT/SOLVATE (PARENT)