orally bioavailable CD73 inhibitor
single agent, dose-dependent antitumor efficacy in mice
opt. of known CD73 inhibitor
J. Med. Chem., December 18, 2022
Calithera Biosciences, South San Fransisco, CA
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…