Design, synthesis, biological evaluation and cellular imaging of imidazo[4,5-b]pyridine derivatives as potent and selective TAM inhibitors.
Basic Information
ID: ALA4261615
Journal: Bioorg Med Chem
Title: Design, synthesis, biological evaluation and cellular imaging of imidazo[4,5-b]pyridine derivatives as potent and selective TAM inhibitors.
Authors: Baladi T, Aziz J, Dufour F, Abet V, Stoven V, Radvanyi F, Poyer F, Wu TD, Guerquin-Kern JL, Bernard-Pierrot I, Garrido SM, Piguel S.
Abstract: The TAM kinase family arises as a new effective and attractive therapeutic target for cancer therapy, autoimmune and viral diseases. A series of 2,6-disubstituted imidazo[4,5-b]pyridines were designed, synthesized and identified as highly potent TAM inhibitors. Despite remarkable structural similarities within the TAM family, compounds 28 and 25 demonstrated high activity and selectivity in vitro against AXL and MER, with IC50 value of 0.77 nM and 9 nM respectively and a 120- to 900-fold selectivity. We also observed an unexpected nuclear localization for compound 10Bb, thanks to nanoSIMS technology, which could be correlated to the absence of cytotoxicity on three different cancer cell lines being sensitive to TAM inhibition.
CiteXplore: 30309671
DOI: 10.1016/j.bmc.2018.09.031
Patent ID: ┄