BI-D1870

Although the initial paper was excellent, and many studies have used this compound to uncover interesting biology, more data has come to light recently. A recent paper discloses a new RSK inhibitor, and they collected data that shows BI-D1870 has more off target kinase activities than a best in class chemical probe should have. This extra information can be found in the supplemental material from this paper: http://www.ncbi.nlm.nih.gov/pubmed/24554780. LJI308 may be more suitable as a probe for the RSKs. In my own work I would likely use them both. Another paper points out that many scientists use BI-D1870 at high concentrations (10 uM), and when used side by side with another RSK compound (SL0101), different results emerge in different systems, suggesting off target activities. This paper is found here: http://www.ncbi.nlm.nih.gov/pubmed/25889895. This compound may be useful for exploration of RSK biology in some contexts if used carefully (lower concentrations), but recent work has demonstrated that it completely inhibits quite a few kinases in vitro at 10 uM. These results complicate its use as a chemical probe and means more experiments need to be done to understand the involvement of the RSKs in the biological process in question. If BI-D1870 is used in a cellular assay, the concentration should be kept lower than 1 uM or multiple kinases will be inhibited. One should also use other inhibitors such as LJI308, and target knockdown to validate findings.

I agree with the previously posted comments. In addition to LJI308, analog LJH685 has been co-crystallized with RPS6KA3 N-terminal domain (pdb 4nus). However, commercial availability is unknown as of this date.