alisertib   Click here for help

GtoPdb Ligand ID: 7790

Synonyms: MLN-8237
PDB Ligand
Compound class: Synthetic organic
Comment: Alisertib is a second generation, orally bioavailable and selective Aurora kinase A inhibitor.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 105.93
Molecular weight 518.12
XLogP 5.03
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES COc1cccc(c1C1=NCc2c(c3c1cc(Cl)cc3)nc(nc2)Nc1ccc(c(c1)OC)C(=O)O)F
Isomeric SMILES COc1cccc(c1C1=NCc2c(c3c1cc(Cl)cc3)nc(nc2)Nc1ccc(c(c1)OC)C(=O)O)F
InChI 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)
InChI Key ZLHFILGSQDJULK-UHFFFAOYSA-N
No information available.
Summary of Clinical Use Click here for help
Alisertib was in Phase 2I clinical development for the treatment of relapsed/refractory peripheral T-cell lymphoma (NCT01482962), but this study has been terminated (May 2015). A Phase 2 study for unresectable stage III-IV melanoma (NCT01316692) is still ongoing.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Since Aurora kinase A localises to spindle poles and spindle microtubules during mitosis, it is thought to regulate spindle assembly. Aberrant expression of Aurora kinases occurs in a wide variety of cancers, including colon and breast cancers. Inhibition of Aurora kinase A by alicertib appears to disrupt the assembly of the mitotic spindle apparatus culminating in the reduced cellular proliferation [1,3].