HPK1i

HPK1i refers to a class of small molecule inhibitors targeting Hematopoietic Progenitor Kinase 1 (HPK1), also known as MAP4K1. HPK1 is a Ste20-related serine/threonine kinase primarily expressed in hematopoietic cells, where it acts as a negative regulator of T-cell receptor (TCR), B-cell receptor (BCR), and dendritic cell signaling. Inhibition of HPK1 is an emerging strategy in cancer immunotherapy designed to enhance anti-tumor immune responses by promoting T-cell activation, increasing the production of effector cytokines (such as IFN-γ and TNF-α), and reducing T-cell exhaustion. Research presented at ASH 2024 demonstrates that HPK1 inhibitors can synergize with the BCL2 inhibitor venetoclax to suppress acute myeloid leukemia (AML) by co-activating cell death pathways and enhancing cytotoxic T-cell responses. Key assets in this class include CFI-402411 (developed by Treadwell Therapeutics) and BGB-15025 (developed by BeiGene).

Other names

HPK1 inhibitorHPK-1 inhibitorHPK 1 inhibitorHematopoietic progenitor kinase 1 inhibitor