Cancer

Cell culture and mouse studies identified an imidazoquinolinone-based ATM inhibitor that could help treat colorectal cancer or triple-negative breast cancer (TNBC) in combination with Camptosar irinotecan or Lynparza olaparib, respectively. In silico screening of a compound library, followed by chemical synthesis and cell-based activity assays of screening hits, yielded an imidazoquinolinone analog (AZD0156) that inhibited ATM with an IC₅₀ of 0.57 nM. In a xenograft mouse model of colorectal cancer, daily oral 20 mg/kg doses of the compound plus weekly intraperitoneal injections of 50 mg/kg Camptosar decreased tumor volume compared with Camptosar alone. In a patient-derived xenograft (PDX) mouse model of TNBC, daily oral 5 mg/kg doses of AZD0156 plus 50 mg/kg doses of Lynparza decreased tumor volume compared with Lynparza alone. Ongoing work by AstraZeneca plc includes Phase I testing of AZD0156 in combination with Camptosar or Lynparza in solid tumors.

Yakult Honsha Co. Ltd. and Pfizer Inc. market Camptosar to treat colorectal cancer and non-small cell lung cancer (NSCLC)...