molecules of the month

What is it? Compound 49 is an orally available CD73 inhibitor with dose-dependent PK/PD and an immune-mediated antitumor mechanism of action. The molecule is highly potent in human plasma (0.38 nM), and despite having a high free fraction (42% unbound) and possessing several highly polar or charged groups, rings, hydrogen bond acceptors and donors, is orally available with a long half-life in rodents. Given the recently approved liquidation of Calithera, development will need to continue by a different company. Why do we care? Calithera is a Bay Area company that focused on programs for immuno-oncology and targeted oncology therapy, including an arginase program (partnered with Incyte) and an oral CD-73 inhibitor program (CB-703, partnered with Antengene). While the structure of…