SHP1‑IN‑2 is a selective and orally active SHP1 inhibitor. SHP1‑IN‑2 covalently binds to Cys480 of SHP1. SHP1‑IN‑2 elicits potent antitumor immunity and suppresses syngeneic tumor growth. SHP1‑IN‑2 blocks tumor progression in a svngeneic cancer model by activating natural killer cells and cytotoxic CD8 ＋ T cells, along with reduced T cel l. SHP1‑IN‑2 can be used for cancer‑related research [1].
In Vivo, SHP1‑IN‑2 (M029) (25 mg/kg, 100 mg/kg; once daily) significantly suppresses tumor growth in MC38 colon cancer syngeneic mouse models[1]. SHP1‑IN‑2 (25 mg/kg; once daily) increases infiltration and activation of NK cells and CD8+ T cells, reduces the proportion of PD-1+ TIM3+ exhausted T cells in MC38 tumor tissues, shows no obvious toxicity or body weight loss in tumor‑bearing mice, and loses antitumor efficacy in CD8+ T cell‑depleted mice and nude mice[1].
In Vitro, SHP1-IN-2 (M029) (up to 50 μM; 24-72 h) shows no obvious cytotoxicity in Jurkat T, HEK293, MC38, EO771, B16-F10, and Raw264.7 cells[1]. SHP1-IN-2 (0-20 μM; Anti-CD3 Antibody (OKT-3) stimulation for 10 min) enhances the phosphorylation of LCK, PLCγ, and ERK1/2 and promotes IL-2 production in TCR-stimulated Jurkat T cells[1].
References:
[1]. Qu Z, et al. Discovery of a First-in-Class Covalent Allosteric SHP1 Inhibitor with Immunotherapeutic Activity. Angew Chem Int Ed Engl. 2026;65(7):e25126.
In Vivo, SHP1‑IN‑2 (M029) (25 mg/kg, 100 mg/kg; once daily) significantly suppresses tumor growth in MC38 colon cancer syngeneic mouse models[1]. SHP1‑IN‑2 (25 mg/kg; once daily) increases infiltration and activation of NK cells and CD8+ T cells, reduces the proportion of PD-1+ TIM3+ exhausted T cells in MC38 tumor tissues, shows no obvious toxicity or body weight loss in tumor‑bearing mice, and loses antitumor efficacy in CD8+ T cell‑depleted mice and nude mice[1].
In Vitro, SHP1-IN-2 (M029) (up to 50 μM; 24-72 h) shows no obvious cytotoxicity in Jurkat T, HEK293, MC38, EO771, B16-F10, and Raw264.7 cells[1]. SHP1-IN-2 (0-20 μM; Anti-CD3 Antibody (OKT-3) stimulation for 10 min) enhances the phosphorylation of LCK, PLCγ, and ERK1/2 and promotes IL-2 production in TCR-stimulated Jurkat T cells[1].
References:
[1]. Qu Z, et al. Discovery of a First-in-Class Covalent Allosteric SHP1 Inhibitor with Immunotherapeutic Activity. Angew Chem Int Ed Engl. 2026;65(7):e25126.