An Exceptionally Potent Inhibitor of Human CD73
journal contributionposted on 22.07.2019, 15:10 by Christine E. Bowman, Rafael G. da Silva, Amber Pham, Stephen W. Young
We recently reported the initiation of a Phase I clinical trial with AB680, a potent human CD73 inhibitor, being developed for the treatment of solid tumors (NCT03677973). We undertook a detailed kinetic analysis of the interaction between human CD73 and AB680 to determine the mode of inhibition. We found AB680 to be a reversible, slow-onset competitive inhibitor of human CD73 with a Ki of 5 pM. Clinical candidates of this potency are uncommon and deserve special consideration during lead optimization.