PROTAC HPK1 Degrader-3

PROTAC HPK1 Degrader-3 (compound C3) is an orally effective PROTAC targeting HPK1 (DC50=21.26 nM) . HPK1 is a negative regulator of T cell receptors, which can lead to T cell dysfunction after abnormal activation. PROTAC HPK1 Degrader-3 can inhibit SLP76 and NF-κB signaling pathways and inhibit MAPK signal transduction, and has anticancer activity and immune activation. PROTAC HPK1 Degrader-3 has a certain oral bioavailability and can be combined with PD-L1 antibody therapy to achieve a tumor growth inhibition rate of 65.58%. PROTAC HPK1 Degrader-3 is composed of E3 ligase ligand Thalidomide (HY-14658; blue part), PROTAC linker tert-Butyl 3-oxoazetidine-1-carboxylate (HY-40146; black part), and target protein ligand HPK1-IN-51 (HY-162842; red part) ; the activity control of the target protein ligand can be HPK1 ligand 1 (HY-162841) [1].