BLU-6348

BLU-6348 is a potent, selective, and orally bioavailable small molecule inhibitor of Hematopoietic Progenitor Kinase 1 (HPK1, also known as MAP4K1), developed by Blueprint Medicines in collaboration with Roche. HPK1 is a serine/threonine kinase that acts as a negative regulator of T-cell receptor (TCR) signaling and immune cell activation. By inhibiting HPK1, BLU-6348 enhances TCR-mediated signaling, leading to increased cytokine production (such as IL-2 and IFNγ) and T-cell proliferation. In preclinical studies, BLU-6348 has demonstrated anti-tumor activity both as a monotherapy and in combination with checkpoint inhibitors like anti-PD-L1, particularly by increasing intratumoral CD8+ T-cell infiltration and improving the effector phenotype of immune cells.