GS-493, a highly specific protein tyrosine phosphatase SHP2 (PTPN11) inhibitor, exhibits remarkable potency with an IC50 of 71 nM. It displays 29- and 45-fold greater affinity towards SHP2 compared to its related counterparts, SHP1 and PTP1B, respectively. In addition, GS-493 impedes both cellular motility and growth of cancer cells, portraying promising antitumor effects.

PTP1B:3.17 μM (IC50), SHP1:2.08 μM (IC50), SHP2:71 nM (IC50)

GS-493, at concentrations ranging from 0.0625 to 10 μM, inhibits hepatocyte growth factor (HGF)-induced epithelial-mesenchymal transition in human pancreatic adenocarcinoma (HPAF) cells[1]. When administered at 40 μM for several days, it significantly reduces growth and decreases the colony formation of the human non-small cell lung cancer (NSCL) cell line LXFA 526L in soft agar to 32%[1].

GS-493, administered intraperitoneally at a dosage of 46 mg/kg daily for 27 days, significantly inhibits tumor growth in a murine xenograft model using NMRI nu/nu mice[1]. This dosage equates to 45.93 mg in 3 mL DMSO per kg. The result indicates a substantial reduction in tumor growth.