PROTAC HPK1 Degrader-3

• UNSPSC Description:

  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].

• Target Antigen:

  MAP4K; PROTACs

• Type:

  Reference compound

• Related Pathways:

  MAPK/ERK Pathway;PROTAC

• Applications:

  Cancer-Kinase/protease

• Field of Research:

  cancer

• Assay Protocol:

  https://www.medchemexpress.com/protac-pd-l1-degrader-2.html

• Smiles:

  CN(C(C(C=CC(C1=CNC2=C1N=C(C=N2)C3=CC=C(C=C3)C4CCN(CC4)C5CN(C6=CC=C7C(C(N(C7=O)C8C(NC(CC8)=O)=O)=O)=C6)C5)=C9)=C9C)=O)C

• Molecular Weight:

  750.84

• References & Citations:

  [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.

• Shipping Conditions:

  Room temperature

• Clinical Information:

  No Development Reported