GSK3179106

GSK3179106 is an orally active and selective RET kinase inhibitor with IC₅₀s of 0.4 nM, 0.2 nM for human RET and rat RET, respectively. GSK3179106 has the potential for irritable bowel syndrome (IBS) through the attenuation of post-inflammatory and stress-induced visceral hypersensitivity^[1]. IC50 & Target: IC50: 0.4 nM (human RET), 0.2 nM (rat RET)^[1] In Vitro: GSK3179106 (10 nM-100 µM; 8 days for TT cells, 3 days for SK-N-AS and A549 cells) inhibits the proliferation of the RET-dependent TT cell line with a mean IC₅₀ value of 25.5 nM however has no effect on the proliferation of the RET-independent SK-NAS and A549 cell lines (mean IC₅₀>10 µM and IC₃₀>17 µM, respectively)^[1].
GSK3179106 inhibits RET phosphorylation in SK-N-AS cells and TT cells with mean IC₅₀s of 4.6 nM and 11.1 nM, respectively^[1]. In Vivo: GSK3179106 (3 or 10 mg/kg; orally; for 3.5 days BID) reduces the visceromotor response (VMR) in comparison to rats given an acetic acid enema and dosed with vehicle^[1].