IC50: 6 nM, 5 nM and 4 nM for the biochemical activities of RSK1, RSK2, and RSK3, respectively

LJH685 is a RSK (p90 ribosomal S6 kinase) inhibitor.

The p90 ribosomal S6 kinase (RSK) family of serine/threonine kinases is found to be expressed in a variety of cancers and its substrate phosphorylation has been implicated in direct regulation of cell proliferation, cell survival, as well as cell polarity.

In vitro: In a previous study, the structural analysis results confirmed the binding of LJH685 to the RSK2 N-terminal kinase ATP-binding site, which suggested that the inhibitor LJH685 adopted an unusual nonplanar conformation that explained its excellent selectivity for RSK family kinases. In addition, LJH685 and it analog LJI308 could efficiently inhibit RSK activity in vitro and in cells. Moreover, in a subset of examined cell lines, the cellular inhibition of RSK and its phosphorylation of YB1 on Ser102 were found to be closely associate with the inhibition of cell growth in an anchorage-independent growth setting [1].

In vivo: So far, there is no animal in vivo data reported for LJH685.

Clinical trial: Up to now, LJH685 is still in the preclinical development stage.

Reference:
[1] Aronchik I, Appleton BA,Basham SE,Crawford K,Del Rosario M,Doyle LV,Estacio WF,Lan J,Lindvall MK,Luu CA,Ornelas E,Venetsanakos E,Shafer CM,Jefferson AB.  Novel potent and selective inhibitors of p90 ribosomal S6 kinase reveal the heterogeneity of RSK function in MAPK-driven cancers. Mol Cancer Res.2014 May;12(5):803-12.