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Design, Synthesis and Biological Evaluation of a Series of Novel Axl Kinase Inhibitors.

ABSTRACT: The receptor tyrosine kinase AXL has emerged in recent years as an potential oncology target due to its over expression in several types of cancers coupled with its ability to promote tumor growth and metastasis. In order to identify small molecule inhibitors of AXL, we built a homology model of its catalytic domain to virtually screen and identify scaffolds displaying an affinity for AXL. Further computational and structure-based design resulted in the synthesis of a series of 2,4,5-trisubstitued pyrimidines which demonstrated potent inhibition of AXL in vitro (IC(50) 19 nM) and strongly inhibited the growth of several pancreatic cell lines.

SUBMITTER: Mollard A

PROVIDER: S-EPMC3254106 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Design, Synthesis and Biological Evaluation of a Series of Novel Axl Kinase Inhibitors.

Mollard Alexis A Warner Steven L SL Call Lee T LT Wade Mark L ML Bearss Jared J JJ Verma Anupam A Sharma Sunil S Vankayalapati Hariprasad H Bearss David J DJ

ACS medicinal chemistry letters 20111201 12

The receptor tyrosine kinase AXL has emerged in recent years as an potential oncology target due to its over expression in several types of cancers coupled with its ability to promote tumor growth and metastasis. In order to identify small molecule inhibitors of AXL, we built a homology model of its catalytic domain to virtually screen and identify scaffolds displaying an affinity for AXL. Further computational and structure-based design resulted in the synthesis of a series of 2,4,5-trisubstitu ...[more]

PMID: 22247788

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