SHP2 protein degrader-1

SHP2 protein degrader-1 is a potent allosteric inhibitor of SHP2. SHP2 protein degrader-1 induces SHP2 degradation and cell apoptosis. SHP2 protein degrader-1 has the potential for researching SHP2 related diseases[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Metabolic Enzyme/Protease >> Phosphatase

Signaling Pathways >> PROTAC >> PROTAC

SHP2[1]

SHP2 protein degrader-1 (compound SP4) (0-200 μM; 24 hours) inhibits the growth of Hela cells, with IC50 of 5.77 and 4.30 nM, respectively, which are about 100 times higher than the activity of SHP099 (SHP2 inhibitor)[1]. SHP2 protein degrader-1 (compound SP4) (0-200 μM; 96 hours) induces 54.01% apoptotic death compared with 0.13% of the control at 100 nM[1]. SHP2 protein degrader-1 (compound SP4) (0-200 μM; 96 hours) induces cell cycle arrested at the G1 phase in Hela cells[1]. SHP2 protein degrader-1 (compound SP4) (0-200 μM; 96 hours) significantly inhibits the phosphorylation of JNK, Erk and p38[1]. SHP2 protein degrader-1 (compound SP4) (0-200 μM; 96 hours) inhibits RAS/MAPK signaling and cellular responses by a mechanism involving inhibition of SHP2 catalytic activity[1]. Cell Viability Assay[1] Cell Line: Hela cells Concentration: 0-200  μM Incubation Time: 24 hours Result: Strongly inhibited the growth of Hela cells, with IC50 of 5.77 and 4.30 nM, respectively, which were about 100 times higher than the activity of SHP099 (SHP2 inhibitor). Apoptosis Analysis[1] Cell Line: Hela cells Concentration: 0-100  μM Incubation Time: 96 hours Result: Induced 54.01% apoptotic death compared with 0.13% of the control at 100 nM. While SHP099 at 1000 nM could induce 33.74% apoptotic death compared with 0.13% of the control. Cell Cycle Analysis[1] Cell Line: Hela cells Concentration: 0-100  μM Incubation Time: 96 hours Result: Induced cell cycle arrested at the G1 phase in Hela cells. Western Blot Analysis[1] Cell Line: Hela cells Concentration: 0-100  μM Incubation Time: 96 hours Result: Significantly inhibited the phosphorylation of JNK, Erk and p38.

[1]. Zheng M, et al. Novel PROTACs for degradation of SHP2 protein. Bioorg Chem. 2021;110:104788.