Ic50 Unit 1 Term Paper

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IC50: 0.004 to 0.013 mMfor 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 about0.004 - 0.013 mmol/L. 10 μMLJI308 could bind to nearly 100% of theRSK2. LJI308 boundtheN-terminiofRSK1, 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 growthwith a different sensitivity[1]. In HTRY-LT cell lines,treating withLJI308 (1-10 µM) after4 or 8 days decreased the cellviability by up to 90%; while little to no effect wasobserved in the non-tumorigenic HTRZ cells [2].

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