PROTAC HPK1 Degrader-3 

PROTAC PD-L1 degrader-2 (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 PD-L1 degrader-2 can inhibit SLP76 and NF-κB signaling pathways and inhibit MAPK signal transduction, and has anticancer activity and immune activation. PROTAC PD-L1 degrader-2 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 PD-L1 degrader-2 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].

MAP4K1/HPK1^[1]

750.84

C₄₃H₄₂N₈O₅

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Wu M, et al. Discovery of an Exceptionally Orally Bioavailable and Potent HPK1 PROTAC with Enhancement of Antitumor Efficacy of Anti-PD-L1 Therapy. J Med Chem. 2024 Aug 22;67(16):13852-13878.  [Content Brief]