Quemliclustat (AB-680): A Comprehensive Profile of a First-in-Class CD73 Inhibitor for Oncologic Indications

Executive Summary

Quemliclustat, also known by its development code AB-680, is an investigational, first-in-class, small-molecule therapeutic agent designed as a potent, selective, and reversible inhibitor of the ectoenzyme CD73 (cluster of differentiation 73).[1] Developed by Arcus Biosciences in collaboration with Gilead Sciences and Taiho Pharmaceutical, Quemliclustat represents a strategic intervention in the field of immuno-oncology, targeting the immunosuppressive adenosine axis within the tumor microenvironment (TME).[4] The fundamental mechanism of action involves the direct inhibition of CD73-mediated conversion of adenosine monophosphate (AMP) to adenosine, a nucleoside that has emerged as a critical mediator of immune evasion in a wide range of malignancies.[1] By blocking this final and rate-limiting step in extracellular adenosine production, Quemliclustat is designed to reverse adenosine-mediated lymphocyte suppression, thereby restoring and enhancing the anti-tumor activity of cytotoxic T-lymphocytes, natural killer (NK) cells, and other key immune effectors.[1]