BMS-986664

BMS-986664 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. Diacylglycerol kinases (DGKs) are enzymes that convert diacylglycerol (DAG) into phosphatidic acid (PA). In the context of T-cell signaling, DAG is a vital second messenger that facilitates T-cell receptor (TCR) mediated activation. By inhibiting DGKα and DGKζ, BMS-986664 prevents the rapid metabolism of DAG, thereby sustaining TCR signaling, enhancing T-cell effector functions, and potentially reversing T-cell exhaustion within the immunosuppressive tumor microenvironment. The compound is being investigated as both a monotherapy and in combination with the PD-1 inhibitor nivolumab to improve clinical outcomes in patients with refractory solid malignancies.