BMS-986528

BMS-986528 is a small molecule inhibitor of diacylglycerol kinase zeta (DGKζ) that was developed by Bristol Myers Squibb for the treatment of refractory, difficult-to-treat rheumatoid arthritis (RA). Diacylglycerol kinases (DGKs) are enzymes that regulate the levels of diacylglycerol (DAG) and phosphatidic acid, which are key signaling lipids in T-cell activation. By inhibiting DGKζ, the drug aims to modulate T-cell receptor signaling pathways. While DGKζ inhibitors are more commonly associated with immuno-oncology for their ability to enhance T-cell responses, BMS-986528 was specifically investigated for its potential to address immune dysregulation in autoimmune diseases. A Phase 1/2a clinical trial (NCT05341453) was conducted in patients with refractory RA, but the development program was terminated by the sponsor in 2023 for strategic reasons.