Design, synthesis, and biological evaluation of novel HPK1 inhibitors possessing 3-cyano-quinoline moiety.

Hematopoietic progenitor kinase 1 (HPK1), a negative regulator of T cell receptor signaling, plays a crucial role in multiple cellular immune responses. Emerging researches have demonstrated that inhibiting HPK1 kinase function enhances T cells' ability to recognize tumor antigens and boosts anti-tumor immune responses. As a result, HPK1 has become a promising target for tumor immunotherapy.

Recent advances of vacuolar protein-sorting 34 inhibitors targeting autophagy.

Autophagy is a ubiquitous pathological/physiological antioxidant cellular reaction in eukaryotic cells. Vacuolar protein sorting 34 (Vps34 or PIK3C3), which plays a crucial role in autophagy, has received much attention. As the only Class III phosphatidylinositol-3 kinase in mammals, Vps34 participates in vesicular transport, nutrient signaling and autophagy.