SHP2-D26 is a highly potent and effective SHP2 degrader. Its mechanism of action involves the induction of SHP2 degradation through binding to VHL-1 and SHP2 proteins. Additionally, the degradation of SHP2 induced by SHP2-D26 is dependent on neddylation and proteasome activity.

SHP2-D26 (0, 3, 10, 30, 100, 300 nM; 12 hours) effectively reduces SHP2 protein in a dosedependent manner, with DC 50 values of 6.0 nM, 2.6 nM in KYSE520 and MV-4-11 cells, respectively[1]. SHP2-D26 (100 nM; 0, 2, 4, 8, 12, 24 hours) reduces the SHP2 protein level within 4 h and completes SHP2 depletion with 8 h in KYSE520 and MV-4-11 cells[1]. SHP2-D26 (0-100 μM for KYSE520 cells; 0-10 nM for MV-4-11 cells; 4 days) achieves IC 50 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 IC 50 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 DC 50 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.