Rsk3 Inhibitors

Chemical inhibitors of Rsk3 function by impeding its kinase activity, which is essential for its role in phosphorylation events within cells. SL 0101-1 achieves this by directly blocking the ATP binding site of Rsk3, thereby preventing the phosphorylation process that Rsk3 would normally facilitate. Similarly, BI-D1870 acts as a potent inhibitor of Rsk3 by obstructing its substrate binding, leading to an overall inhibition of Rsk3 kinase activity and its subsequent signaling pathways. LJH685 also targets Rsk3, but it does so by interfering within the ATP-binding pocket of the kinase, which is crucial for its activity. FMK takes a slightly different approach by forming a covalent bond with the kinase domain of Rsk3, thus irreversibly inhibiting its function by preventing ATP from binding.

Continuing with the inhibition mechanisms, LJI308 operates by allosterically modulating the kinase domain of Rsk3, which results in dampened kinase activity. PF-4708671 is another selective inhibitor of S6K1 that can indirectly affect Rsk3 kinase activity through its impact on the AGC kinase pathway. Fasudil, known as a Rho-kinase inhibitor, can also indirectly inhibit Rsk3 through its effects on the RhoA/ROCK pathway, which interacts with the Rsk pathway. H-89 acts upon protein kinase A (PKA) and through the crosstalk between PKA and Rsk signaling pathways, the inhibition of PKA can lead to a reduction in the activation of Rsk3. Lastly, LY294002 and Wortmannin, both PI3K inhibitors, can indirectly inhibit Rsk3 by targeting the PI3K/Akt pathway, which is upstream of Rsk3 and necessary for its activation.