Home » Key Drug Discovery Articles » Computer aided drug discovery of highly ligand efficient, low molecular weight imidazopyridine analogs as FLT3 inhibitors

Computer aided drug discovery of highly ligand efficient, low molecular weight imidazopyridine analogs as FLT3 inhibitors

Significance Statement

The FLT3 kinase represent an attractive target to effectively treat AML.  Unfortunately, no FLT3 targeted therapeutic is currently approved.  In line with our continued interests in treating kinase related disease, we utilized pioneering synthetic methodology in combination with computer aided drug discovery and identified low molecular weight, highly ligand efficient, FLT3 kinase inhibitors.  Compounds were analyzed for biochemical inhibition, their ability to selectively inhibit cell proliferation, for FLT3 mutant activity, and preliminary aqueous solubility.  Validated hits were discovered that can serve as starting platforms for lead candidates.

Figure Legend: FLT3 hit generation was accomplished using pioneering synthetic methodology in combination with computer aided drug discovery.  In silico hits were progressed to biochemical and cell-based assays.

Computer aided drug discovery of highly ligand efficient, low molecular weight imidazopyridine analogs as FLT3 inhibitors. Global Medical Discovery

 

 

 

 

Journal Reference

Frett B1, McConnell N1, Smith CC2, Wang Y1, Shah NP3, Li HY4. Eur J Med Chem. 2015 Apr 13;94:123-31.

1College of Pharmacy, Department of Pharmacology and Toxicology, The University of Arizona, Tucson, AZ 85721, USA.

2Division of Hematology/Oncology, University of California, San Francisco, CA, USA.

3Division of Hematology/Oncology, University of California, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.

4College of Pharmacy, Department of Pharmacology and Toxicology, The University of Arizona, Tucson, AZ 85721, USA; The University of Arizona Cancer Center, 1515 N Campbell Ave, Tucson, AZ 85724, USA. Electronic address: [email protected]

Abstract

The FLT3 kinase represents an attractive target to effectively treat AML. Unfortunately, no FLT3 targeted therapeutic is currently approved. In line with our continued interests in treating kinase related disease for anti-FLT3 mutant activity, we utilized pioneering synthetic methodology in combination with  computer aided drug discovery and identified low  molecular  weight,  highly  ligand efficient,  FLT3 kinase inhibitors. Compounds were analyzed for biochemical inhibition, their ability to selectively inhibit cell proliferation, for FLT3 mutant activity, and preliminary aqueous solubility. Validated hits were discovered that can serve as starting platforms for lead candidates.

Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Go To European Journal of Medicinal Chemistry

 

 

 

 

 

 

 

 

Global Medical Discovery Company