HPK1 (417)

Hematopoietic progenitor kinase 1 (HPK1), also referred to as MAP4K1, belongs to the mammalian Ste20-like family of serine/threonine kinases and functions through the JNK and ERK signaling pathways. As a negative immune regulator of T cell receptor (TCR) and B cell signaling, HPK1 is predominantly expressed in hematopoietic cells. Research utilizing HPK1 kinase-dead knock-in mouse models has revealed that HPK1 kinase activity restricts TCR signaling and cytokine production. In preclinical syngeneic models, the loss of HPK1 kinase activity was shown to inhibit tumor growth. These discoveries have established HPK1 as a promising target for anti-cancer immunotherapy. Consequently, the development of small molecule inhibitors targeting HPK1 presents a potential therapeutic approach for cancer and other related conditions.