Discovery of a stable macrocyclic o-aminobenzamide Hsp90 inhibitor which significantly decreases tumor volume in a mouse xenograft model.
Basic Information
ID: ALA1806368
Journal: Bioorg Med Chem Lett
Title: Discovery of a stable macrocyclic o-aminobenzamide Hsp90 inhibitor which significantly decreases tumor volume in a mouse xenograft model.
Authors: Zapf CW, Bloom JD, Li Z, Dushin RG, Nittoli T, Otteng M, Nikitenko A, Golas JM, Liu H, Lucas J, Boschelli F, Vogan E, Olland A, Johnson M, Levin JI.
Abstract: An extension of our previously reported series of macrocyclic ortho-aminobenzamide Hsp90 inhibitors is reported. Addition of a second methyl group to the tether provided analogs that show increased potency in binding as well as cell-proliferation assays and, more importantly, are stable toward microsomes. We wish to disclose the discovery of a macrocycle which showed impressive biomarker activity 24-h post dosing and which demonstrated prolonged exposure in tumors. When studied in a lung cancer xenograft model, the compound demonstrated significant tumor size reduction.
CiteXplore: 21715165
DOI: 10.1016/j.bmcl.2011.05.102
Patent ID: ┄