Rsk-3 Inhibitors

RSK-3 inhibitors encompass a range of chemicals that either directly target RSK-3 or indirectly influence its activity by modulating upstream signaling pathways. RSK-3, as part of the RSK family, plays a crucial role in cell growth, survival, and proliferation, primarily through the phosphorylation of downstream substrates following activation by the ERK/MAPK pathway. Direct inhibitors such as BI-D1870, SL 0101-1, and FMK are designed to interfere with the kinase activity of RSK-3. BI-D1870, for instance, is a potent inhibitor that acts across various RSK isoforms, including RSK-3, by obstructing the ATP-binding site essential for kinase activity. SL 0101-1 specifically targets RSK-3 and impedes its function by binding to its ATP-binding site, rendering it inactive. Indirect inhibitors like ERK Inhibitor II, PD 98059, U0126, LY3214996, SCH772984, Cobimetinib, and Trametinib target upstream components of the signaling cascade leading to RSK-3 activation. These inhibitors typically focus on the MEK/ERK pathway, which is critical for RSK-3 activation. By inhibiting MEK or ERK, these compounds effectively reduce RSK-3 activity. For example, PD 98059 and U0126 are well-known MEK inhibitors, thereby hindering the MEK-ERK-RSK-3 axis. LY3214996 and SCH772984, as selective ERK inhibitors, prevent the downstream activation of RSK-3.