Optimization of a novel kinase inhibitor scaffold for the dual inhibition of JAK2 and FAK kinases

Craig A Zificsak; Diane E Gingrich; Henry J Breslin; Derek D Dunn; Karen L Milkiewicz; Jay P Theroff; Tho V Thieu; Ted L Underiner; Linda R Weinberg; Lisa D Aimone; Mark S Albom; Jennifer L Mason; Lisa Saville; Jean Husten; Thelma S Angeles; James P Finn; Mahfuza Jan; Teresa M O'Kane; Pawel Dobrzanski; Bruce D Dorsey

doi:10.1016/j.bmcl.2011.11.049

Optimization of a novel kinase inhibitor scaffold for the dual inhibition of JAK2 and FAK kinases

Bioorg Med Chem Lett. 2012 Jan 1;22(1):133-7. doi: 10.1016/j.bmcl.2011.11.049. Epub 2011 Nov 25.

Affiliation

¹ Worldwide Discovery Research, Cephalon, Inc., 145 Brandywine Parkway, West Chester, PA 19380, USA. czificsa@cephalon.com

PMID: 22169263
DOI: 10.1016/j.bmcl.2011.11.049

Abstract

The elaboration of a novel scaffold for the inhibition of JAK2 and FAK kinases was targeted in order to provide a dual inhibitor that could target divergent pathways for tumor cell progression.

MeSH terms

Animals
Cell Line, Tumor
Chemistry, Pharmaceutical / methods
Disease Progression
Drug Design
Focal Adhesion Protein-Tyrosine Kinases / chemistry*
Humans
Inhibitory Concentration 50
Janus Kinase 2 / chemistry*
Mice
Models, Chemical
Mutation
Neoplasms / genetics
Neoplasms / pathology
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / pharmacology*
Rats
Rats, Sprague-Dawley
Signal Transduction
Time Factors

Substances

Protein Kinase Inhibitors
Focal Adhesion Protein-Tyrosine Kinases
Janus Kinase 2