molecules of the month

The Zentalis Wee1 inhibitor, ZN-c3, is a highly selective kinase inhibitor that is currently being evaluated in Ph. II clinical trials in adult women with recurrent or persistent uterine serous carcinoma (USC). The starting pyrazolopyrimidinone series was from the WO2013126656 patent, and while the molecule is similar to other kinase inhibitors (e.g. adavosertib, AZD1775), the ethyl group of the tertiary alcohol provided an unexpected improvement of potency while allowing maintenance of other properties including intrinsic clearance. It is an interesting example of navigating tight IP space to find a development candidate.