PROTAC SHP2 degrader-1

PROTAC SHP2 degrader-1 is a potent and effective SHP2 degrader. PROTAC SHP2 degrader-1 induces SHP2 degradation requires binding to VHL-1 and SHP2 proteins and is also neddylation- and proteasome-dependent[1].

Research Areas >> Cancer

Signaling Pathways >> Metabolic Enzyme/Protease >> Phosphatase

PROTAC SHP2 degrader-1 (0, 3, 10, 30, 100, 300 nM; 12 hours) effectively reduces SHP2 protein in a dosedependent manner, with a DC50 values of 6.0 and 2.6 nM in KYSE520 and MV-4-11 cells, respectively[1]. PROTAC SHP2 degrader-1 (100 nM; 0, 2, 4, 8, 12, 24 hours) reduces the SHP2 protein level within 4 h and complete SHP2 depletion with 8 h in KYSE520 and MV-4-11 cells[1]. PROTAC SHP2 degrader-1 (0-100 μM for KYSE520 cells; 0-10 nM for MV-4-11 cells；4 days) achieves IC50 values of 0.66 μM, 0.99 nM in KYSE520 and MV-4-11 cells, respectively[1]. Cell Proliferation Assay[1] Cell Line: KYSE520 and MV-4-11 cells Concentration: 0-100 μM for KYSE520 cells; 0-10 nM for MV-4-11 cells Incubation Time: 4 days Result: Achieved IC50 values of 0.66 μM, 0.99 nM in KYSE520 and MV-4-11 cells, respectively. Western Blot Analysis[1] Cell Line: KYSE520 and MV-4-11 cells Concentration: 0, 3, 10, 30, 100, 300 nM Incubation Time: 12 hours Result: Reduced SHP2 protein in a dosedependent manner, with a DC50 values of 6.0 and 2.6 nM in KYSE520 and MV-4-11 cells, respectively. Western Blot Analysis[1] Cell Line: KYSE520 and MV-4-11 cells Concentration: 100 nM Incubation Time: 0, 2, 4, 8, 12, 24 hours Result: Reduced the SHP2 protein level within 4 h and completed SHP2 depletion with 8 h.

[1]. Wang M, et al. Discovery of SHP2-D26 as a First, Potent, and Effective PROTAC Degrader of SHP2 Protein [published correction appears in J Med Chem. 2021 Jan 14;64(1):906-908]. J Med Chem. 2020;63(14):7510-7528.