molecules of the month

Context. AZD7648 (AstraZeneca) is an oral DNA-PK inhibitor. DNA-PK, ATR, and ATM are all kinases involved in DNA damage repair and have been of significant recent interest due to the success of PARP inhibitors and the concept of synthetic lethality. We have highlighted a few DNA-PK inhibitors and ATR inhibitors recently. The discovery of AZD7648 has previously been reported. This recent article highlights the in vivo pharmacology of the molecule in several ovarian cancer patient-derived xenograft (PDX) models, extending prior work, showing in vivo potentiation of activity of olaparib in BRCA- PDXs, but not BRCA+ PDXs, suggesting that an olaparib/DNA-PK inhibitor combination could be effective in ovarian cancer. Two trials involving AZD7648 have been posted and appear to be recruiting.…