Cancer

Cell culture and mouse studies identified a quinazoline-based compound that could help treat c-Kit- and PDGFR-mutant gastrointestinal stromal tumors (GISTs). Chemical synthesis of phenoxyquinazoline- and quinolone-based PDGFRA inhibitors followed by testing in mouse cell-based models of GIST harboring oncogenic c-Kit or PDGFR mutations yielded a compound (AZD3229) that inhibited cell growth with IC₅₀ values of 1-971 nM. In two mouse models of GISTs, the compound decreased tumor volume compared with Gleevec imatinib. Ongoing work by AstraZeneca plc includes testing the PK/PD of AZD3229...