An Exceptionally Potent Inhibitor of Human CD73

Biochemistry. 2019 Aug 6;58(31):3331-3334. doi: 10.1021/acs.biochem.9b00448. Epub 2019 Jul 23.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5'-Nucleotidase / antagonists & inhibitors*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Inhibitory Concentration 50


  • Enzyme Inhibitors
  • 5'-Nucleotidase

Associated data