BMS-986533

BMS-986533 is an investigational, orally bioavailable small molecule inhibitor of diacylglycerol kinase alpha (DGKα) and zeta (DGKζ), developed by Bristol Myers Squibb. DGK enzymes are intracellular kinases that phosphorylate diacylglycerol (DAG) into phosphatidic acid, thereby terminating DAG-mediated signaling. In T cells, DAG is a crucial second messenger downstream of the T-cell receptor (TCR) that activates the RasGRP1/Ras/ERK and PKCθ/NF-κB pathways, which are essential for T-cell activation, proliferation, and cytokine production. By inhibiting DGKα and DGKζ, BMS-986533 sustains DAG levels, enhancing TCR signaling and potentially overcoming the immunosuppressive signals found in the tumor microenvironment. It is currently in early-phase clinical development for the treatment of advanced solid tumors and is being evaluated for safety and pharmacokinetics in healthy volunteers.