vizenpistat

Vizenpistat (SR-8541A) is an orally bioavailable small molecule inhibitor of Ectonucleotide Pyrophosphatase/Phosphodiesterase-1 (ENPP1). ENPP1 acts as a dual metabolic checkpoint by hydrolyzing 2′3′-cyclic GMP-AMP (cGAMP), which prevents the activation of the STING-dependent innate immune response, and by converting ATP and NAD+ into adenosine, a potent immunosuppressor. By inhibiting ENPP1, vizenpistat increases intratumoral cGAMP levels and decreases adenosine production, thereby promoting both innate and adaptive anti-tumor immunity. It is currently under clinical investigation for the treatment of advanced solid tumors and microsatellite stable (MSS) colorectal cancer, both as a monotherapy and in combination with immune checkpoint inhibitors such as botensilimab and balstilimab.