BMS-986453 (Bristol Myers Squibb)

BMS-986453 is an orally bioavailable small molecule inhibitor of diacylglycerol kinase alpha (DGKα) and diacylglycerol kinase zeta (DGKζ), currently under development by Bristol Myers Squibb for the treatment of advanced solid tumors. DGK enzymes, particularly the alpha and zeta isoforms, are highly expressed in T-cells and function as negative regulators of T-cell activation by converting diacylglycerol (DAG)—a key second messenger in T-cell receptor (TCR) signaling—into phosphatidic acid (PA). By inhibiting these enzymes, BMS-986453 maintains elevated levels of DAG, thereby enhancing TCR-mediated signaling and promoting T-cell effector functions and proliferation. This mechanism aims to overcome the immunosuppressive tumor microenvironment and is being investigated both as a monotherapy and in combination with immune checkpoint inhibitors like nivolumab. Clinical trials are currently focusing on patients with non-small cell lung cancer (NSCLC), melanoma, renal cell carcinoma (RCC), and head and neck squamous cell carcinoma (HNSCC).

Other names

diacylglycerol kinase alpha/zeta inhibitorDGK alpha/zeta inhibitor