SHP2 protein degrader-1 is a highly efficient allosteric inhibitor targeting SHP2, inducing its degradation and resulting in cell apoptosis; it shows promising potential for studying diseases associated with SHP2.

SHP2 protein degrader-1 (compound SP4), at concentrations of 0-200 μM over 24 hours, significantly inhibits Hela cell growth with IC50 values of 5.77 and 4.30 nM, demonstrating approximately 100 times greater efficacy than SHP099 (SHP2 inhibitor). When applied at 0-200 μM for 96 hours, compound SP4 induces apoptotic death (54.01%) at 100 nM, compared to 0.13% in the control group. Additionally, this concentration and exposure time result in G1 phase cell cycle arrest and a significant reduction in the phosphorylation of JNK, Erk, and p38. These effects are due to the inhibition of RAS/MAPK signaling by blocking SHP2's catalytic activity, highlighting SP4's potential as a potent inhibitor of cellular growth and pro-apoptotic agent in Hela cells.