FS-694

FS-694 is a dual active “type 1.5” inhibitor for P38-alpha (MAPK14) and P38-beta (MAPK11).  Broad kinase selectivity at 1 µM shows that the compound is extremely selective.  Off target activities include casein kinase 1 epsilon (CSNK1E) which is essentially completely inhibited in the discoverX panel screen at 1 µM, but no activity is seen in follow up in cells at 20 µM.  Some inhibition of P38-gamma is observed – no IC50 is reported but this is likely to be considerably weaker than the alpha/beta inhibition.  Relatively slow binding kinetics are observed with a residence time of around 4 minutes.  It has been previously noted that Type I and Type II kinase inhibitors can lead to different downstream consequences; FS-694 is a Type 1.5 inhibitor.  It is recommended that other tool compounds are used in parallel to check whether different results are obtained, for example Type I: Skepinone-L (related structure to FS-694) and VX-745 (unrelated), Type Il SR-318, BIRB769.  A negative control compound is also available.

According to the literature, the compound is both an efficient probe for the target and has good qualities regarding the observed criteria (potency, selectivity, engagement etc.). However further assays, such as cytotoxicity, should be performed in order to gain insight into its full spectrum of activity.