BioCentury
ARTICLE | Distillery Therapeutics

Cancer

September 27, 2017 6:17 PM UTC

In vitro, cell culture and mouse studies identified two dihydropyrazolopyridine-based dual CREBBP/EP300 inhibitors that could help treat AML and prostate cancer. Chemical synthesis and in vitro binding assays of methylpyrazole-dihydropyrazolopyridine analogs yielded two compounds: GNE-781, which bound CREBBP and EP300 with IC50 values of 0.94 and 1.2 nM, respectively; and GNE-049, which bound CREBBP and EP300 with IC50 values of 1.1 and 2.3 nM, respectively. In a xenograft mouse model of AML, GNE-781 decreased tumor growth compared with vehicle. In a patient-derived xenograft (PDX) mouse model of prostate cancer, GNE-049 decreased tumor growth compared with Xtandi enzalutamide. Next steps by the Genentech Inc. unit of Roche could include testing the compounds in additional models of AML and/or prostate cancer...