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

Brendan Frett, Nick McConnell, Catherine C. Smith, Yuanxiang Wang, Neil P. Shah, Hong Yu Li

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)123-131
Number of pages9
JournalEuropean Journal of Medicinal Chemistry
Volume94
DOIs
StatePublished - Apr 13 2015

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Drug Discovery
Phosphotransferases
Molecular Weight
Molecular weight
Ligands
Cell proliferation
Solubility
Cell Proliferation
Therapeutics

Keywords

  • AML
  • Computer aided drug discovery
  • FLT3
  • Kinase inhibitor
  • Ligand efficiency

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

Computer aided drug discovery of highly ligand efficient, low molecular weight imidazopyridine analogs as FLT3 inhibitors. / Frett, Brendan; McConnell, Nick; Smith, Catherine C.; Wang, Yuanxiang; Shah, Neil P.; Li, Hong Yu.

In: European Journal of Medicinal Chemistry, Vol. 94, 13.04.2015, p. 123-131.

Research output: Contribution to journalArticle

Frett, Brendan ; McConnell, Nick ; Smith, Catherine C. ; Wang, Yuanxiang ; Shah, Neil P. ; Li, Hong Yu. / Computer aided drug discovery of highly ligand efficient, low molecular weight imidazopyridine analogs as FLT3 inhibitors. In: European Journal of Medicinal Chemistry. 2015 ; Vol. 94. pp. 123-131.
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