SHP2-D26 is a first, potent and effective SHP2 degrader. SHP2-D26 induces SHP2 degradation requires binding to VHL-1 and SHP2 proteins. SHP2-D26 is also neddylation- and proteasome-dependent In Vitro 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. 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. 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Proliferation AssayCell 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 AnalysisCell 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 AnalysisCell 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. Form:Solid IC50& Target:SHP2