TPI-1 is a SHP-1 inhibitor.

SHP-1 has been identified as a promising target for cancer therapy. TPI-1, starting at an effective concentration of 10 ng/mL, selectively enhances the phosphorylation of SHP-1 substrates (notably pLck-pY394) in Jurkat T cells, without significantly affecting pERK1/2 or pLck-pY505 levels. Moreover, TPI-1 promotes the induction of IFNγ+ cells both in mouse spleen and human peripheral blood[1], demonstrating its potential selectivity and therapeutic efficacy in a cellular context.

TPI-1 effectively suppresses the growth of B16 melanoma tumors in mice through a mechanism reliant on T cells when administered orally at tolerable doses, yet it demonstrates minimal impact on B16 cell proliferation in vitro. Additionally, TPI-1 enhances the levels of pLck-pY394 and IFNγ+ cells in mice, further contributing to its anti-tumor activity. Notably, TPI-1 also restricts B16 tumor expansion and extends the survival of mice bearing tumors when given as a subcutaneously tolerated agent[1].

Jump-In TI CHO-K cells stably expressing WT or mutant S1P3 are serum-starved for 4 hrs. They are then incubated at 4 °C for 30 min in the binding buffer containing 20 mM Tris-HCl (pH 7.5), 100 mM NaCl, 15 mM NaF, 0.5 mM EDTA, 1 mM Na3VO4, 0.5% fatty acid-free bovine serum albumin, and protease inhibitor mixture with 0.1 nM [33P]S1P and increasing concentrations of S1P, SPM-242, or CYM-5541. Cells are washed three times with cold binding buffer. Cell-bound radioactivity is measured by lysing the cells with 0.5% SDS followed by liquid scintillation counting. The raw data is normalized so that the level of [33P]S1P bound to each cell line (WT or mutant) in the absence of competing ligand is referenced as 100% for its own cell line[1].