tcsc0695 GSK1838705A

GSK1838705A is a potent and reversible IGF-IR and the insulin receptor inhibitor with IC₅₀s of 2.0 and 1.6 nM, respectively. It also inhibits ALK with an IC₅₀ of 0.5 nM.

IC50 & Target: IC50: 2.0 nM (IGF-IR), 1.6 nM (insulin receptor), 0.5 nM (ALK)^[1]

In Vitro: In cellular phosphorylation assays, GSK1838705A potently inhibits IGF-IR and insulin receptor phosphorylation with IC₅₀s of 85 and 79 nM, respectively. ^appK_i values are 0.7 nM for IGF-IR and 1.1 nM for insulin receptor using the filter binding assay. GSK1838705A inhibits the proliferation in a panel of cell lines derived from solid and hematologic tumors. The EC₅₀s of GSK1838705A range from 20 nM to >8 μM, but are <1 μM in most multiple myeloma and Ewing's sarcoma cell lines^[1].

In Vivo: GSK1838705A shows robust antitumor activity in animal xenograft models. Tumor types likely to respond to GSK1838705A include multiple myeloma and Ewing's sarcoma, as well as ALK-driven tumors (e.g., ALCL, NSCLC, and neuroblastoma). A single oral dose of GSK1838705A at 0.1 and 0.3 mg/kg results in 35% and 65% inhibition of IGF-IR phosphorylation, respectively, whereas doses ≥1 mg/kg results in complete inhibition of ligand-induced IGF-IR phosphorylation^[1].