IC50: 0.004 to 0.013 mM for RSK1, 2, and 3.

LJI308 is a potent and selective inhibitor of RSK. The p90 ribosomal S6 kinase (RSK) comprises a family of serine/threonine kinase which is expressed in various human cancers. RSK is the cytosolic substrate for the ERK (extracellular sianal-regulated kinase), involved in direct regulation of cell survival, proliferation, and cell polarity. Previous studies have demonstrated that RSK pathway is important for the growth and proliferation of cancer stem cells [1,2].

The IC50 values of LJI308 against RSK1, 2, and 3 were about 0.004 - 0.013 mmol/L. 10 μM LJI308 could bind to nearly 100% of the RSK2. LJI308 bound the N-termini of RSK1, RSK3, and RSK4 to a similar extent. LJI308 inhibited S6K1 with an IC50 of 0.8 mM. In both MDA-MB-231 and H358 cell lines, 1 μM and 10 μM LJI308 exihibited an inhibitory effect on colony formation and cell growth with a different sensitivity [1]. In HTRY-LT cell lines, treating with LJI308 (1-10 μM) after 4 or 8 days decreased the cell viability by up to 90%; while little to no effect was observed in the non-tumorigenic HTRZ cells [2].

LJI308, the RSK inhibitor, could be used in combination with conventional chemotherapy to overcome the drug resistance and improve survival in patients with the triple-negative breast cancer (TNBC) [2].

References:
[1].Aronchik I, Appleton B A, Basham S E, et al. Novel potent and selective inhibitors of p90 ribosomal S6 kinase reveal the heterogeneity of RSK function in MAPK-driven cancers[J]. Molecular Cancer Research, 2014, 12(5): 803-812.
[2].Davies A H, Reipas K, Hu K, et al. Inhibition of RSK with the novel small-molecule inhibitor LJI308 overcomes chemoresistance by eliminating cancer stem cells[J]. Oncotarget, 2015, 6(24): 20570.