5'-Ectonucleotidase (CD73) inhibitors: a patent review (2021-present).

Abstract

Introduction: Adenosine-mediated immunosuppression is a major mechanism of tumor immune escape and is largely driven by ecto-5'-nucleotidase (CD73), which catalyzes the formation of extracellular adenosine and limits the efficacy of cancer immunotherapies. Consequently, CD73 has emerged as a key immune checkpoint and an attractive target for therapeutic and diagnostic intervention.

Areas covered: This review summarizes patent literature on CD73 inhibitors published from 2021 to the present. The analysis covers advances in nucleotide-derived inhibitors, including structure-guided optimization and strategies enabling peroral bioavailability, as well as the maturation of non-nucleotide small-molecule inhibitors with alternative binding modes. In addition, CD73-targeted antibodies, nanobodies, and positron emission tomography (PET) tracers are discussed in the context of translational development, patient stratification, and combination therapy. Patent databases were systematically surveyed to identify relevant disclosures and emerging trends.

Expert opinion: Recent patents indicate a shift from maximizing enzymatic potency toward balanced optimization of potency, pharmacokinetics, and combinatorial compatibility. Perorally bioavailable small molecules and CD73-targeted imaging agents are positioning CD73 inhibition as a mature and versatile therapeutic and theranostic strategy.