SPI-112

SPI-112 is a potent, selective and competitive SHP2 (PTPN11) inhibitor with IC50s of 1 μM, 18.3 μM and 14.5 μM for SHP2, protein tyrosine phosphatase (PTP) and PTP1B, respectively[1][2].

Research Areas >> Cancer

Signaling Pathways >> Metabolic Enzyme/Protease >> Phosphatase

IC50: 1 μM (SHP2), 18.3 μM (PTP) and 14.5 μM (PTP1B)[2]

SPI-112 has a polar -NO2 or a negatively charged -COOH group and has no detectable cellular activity, suggesting that SPI-112 is not cell permeable[1]. In surface plasmon resonance (SPR) binding assay, SPI-112 displays a 1:1 stoichiometric binding kinetics to SHP2 with a kinetic constant KD of 1.30 µM. Enzyme kinetic data obtained with SPI-112 are best fitted with the competitive inhibition model (Ki of 0.8 µM), suggesting that SPI-112 interacts with the catalytic site of SHP2[1].

[1]. Chen L, et al. Inhibition of cellular Shp2 activity by a methyl ester analog of SPI-112. Biochem Pharmacol. 2010 Sep 15;80(6):801-10.

[2]. Lawrence HR, et al. Inhibitors of Src homology-2 domain containing protein tyrosine phosphatase-2 (Shp2) based on oxindole scaffolds. J Med Chem. 2008 Aug 28;51(16):4948-56.