GTx-134 (GTx 134) is a selective small-molecule inhibitor of IGF-1R and insulin receptor (IR) with biochemical IC50 of 97 nM and 187 nM, respectively.
GTx-134 is selective for IGF-1R and closely related RTKs in a broad survey of the kinome.
GTx-134 (1-5 uM) inhibited IGF-1 induced phosphorylation of IGF-1R and Akt in a dose-dependent manner in HMCL, MM1.S cells, equally inhibited signaling downstream of both IGF-1R and IR.
GTx-134 inhibited the growth of genetically diverse human myeloma cell lines (HMCLs) at low micromolar level (IC50<5 uM), MM1.S, UTMC2, and H929 were most sensitive to the cytotoxic effects of GTx-134 (IC50 < 1.5 uM).
GTx-134 showed in vitro synergies when combined with dexamethasone or lenalidomide.
GTx-134 enhanced the activity of PD173074, a FGFR3 inhibitor, against t(4;14) myeloma cells.
GTx-134 inhibited IGF-1R signaling and induces apoptosis of primary MM cells, GTx-134 (40 mg/kg/day, i.p.)effectively reduced tumor burden in a HMCL xenografts model.