Merck, SML1788-5MG, LJI308

Biochem/physiol Actions
LJI308 is potent pan-RSK inhibitor that targets RSK N-terminal kinase domain (NTKD) ATP-binding site (IC₅₀/[ATP] = 6 nM/5 μM/RSK1, 4 nM/20 μM/RSK2, 13 nM/10 μM/RSK3), exhibiting similary binding affinity toward RSK1-4, but much reduced inhibitory potency against S6K1 (IC₅₀ = 0.8 μM), MEK4 (IC₅₀ >10 μM), and HIP kinase 1 (IC₅₀ >1 μM). LJI308 effectivelfy reduces cellular Y-box binding protein-1 (YB1) Ser102 (EC₅₀ = 0.2-0.3 μM; MDA-MB-231 and H358 cells), but not ribosomal S6 protein (S6RP) S235/236, phosphorylation level and selectively inhibits the growth of YB1-overpressing HTRY-LT triple-negative breast cancer (TNBC) cells, but not the parental non-tumorigenic human mammary epithelial cell (HMEC) line HTRZ (% inhibition = 6.8%/HTRZ, 88%/HTRY-LT1, 66%/HTRY-LT2 in 8 days; 5 μM at 0 and 96 hr).
LJI308 is potent pan-RSK inhibitor that targets RSK N-terminal kinase domain ATP-binding site and inhibits YB1-dependent growth of cncer cells.