BMS-986504

BMS-986504 is an orally bioavailable small molecule inhibitor of diacylglycerol kinase alpha (DGKα) and zeta (DGKζ), currently under development by Bristol Myers Squibb for the treatment of advanced solid tumors. DGKα and DGKζ are enzymes that metabolize diacylglycerol (DAG), a critical second messenger in T-cell activation, into phosphatidic acid. By inhibiting these enzymes, BMS-986504 aims to sustain high levels of DAG at the immunological synapse, thereby enhancing T-cell receptor signaling and effector function. This mechanism is intended to reverse T-cell anergy and exhaustion within the immunosuppressive tumor microenvironment, potentially improving the efficacy of immune checkpoint inhibitors like nivolumab.