SHP1 Inhibitor, TPI-1

TPI-1 is an orally bioavailable, noncytotoxic benzoquinone compound that acts as a potent irreversible inhibitor of SHP-1 (Src homology region 2 domain-containing phosphatase 1) catalytic domain (IC50 ~ 40 nM or 0.01 μg/ml) with selectivity over SHP-2 (IC50 ~ 0.1 μg/ml), MKP1 (IC50 > 1 μg/ml) and CD45. TPI-1 potently induces mouse and human primary IFN-g+ cells both in vitro and in vivo. Effectively inhibits B16 melanoma tumors in mice (1 or 3 mg/kg, s.c., daily) and prolong the survival. TPI-1 is shown to be 50-fold more effective than sodium stibogluconate in cell-based assays and may non-specifically react with cysteine residues.

orally bioavailable, noncytotoxic benzoquinone compound that acts as a potent and selective irreversible inhibitor of SHP-1 catalytic domain