Author/Authors :
Vincent W.-F. Tai، نويسنده , , David Sperandio، نويسنده , , Emma J. Shelton، نويسنده , , Joane Litvak، نويسنده , , Keith Pararajasingham، نويسنده , , Ben Cebon، نويسنده , , Julia Lohman، نويسنده , , John Eksterowicz، نويسنده , , Seema Kantak، نويسنده , , Peter Sabbatini، نويسنده , , Cindy Brown، نويسنده , , Jennifer Zeitz، نويسنده , , Chris Reed ، نويسنده , , Bill Maske، نويسنده , , Doris Graupe، نويسنده , , Alberto Estevez، نويسنده , , Jason Oeh، نويسنده , , Darren Wong، نويسنده , , Yong Ni ، نويسنده , , Paul Sprengeler، نويسنده , , et al.، نويسنده ,
Abstract :
As a continuation of our efforts to discover novel apoptosis inducers as anticancer agents using a cell-based caspase HTS assay, 2-phenyl-oxazole-4-carboxamide derivatives were identified. The structure–activity relationships of this class of molecules were explored. Compound 1k, with EC50 of 270 nM and GI50 of 229 nM in human colorectal DLD-1 cells, was selected and demonstrated the ability to cleave PARP and displayed DNA laddering, the hallmarks of apoptosis. Compound 1k showed 63% tumor growth inhibition in human colorectal DLD-1 xenograft mouse model at 50 mpk, bid.
Keywords :
apoptosis , antitumor , Apoptosis activators , oxazole
