MDI-114215 is a potent, allosteric, and highly selective dual-LIMK1/2 inhibitor with IC50 of 20/27 nM respectively.
MDI-114215 inhibits PAK1-phosphorylated LIMK1/2 activity with pIC50 of 7.89 and 7.96, and reduces cellular p-cofilin levels in the AlphaLISA assay.
MDI-114215 does not bind TESK1, a close neighbor that is a member of the TKL kinase family, nor to CaMKIV, MRCKα, PAK1–2/4 or ROCK1/2.
MDI-114215 decreases phosphorylated cofilin levels ex vivo and reverses the deficit in LTP of mouse Fmr1 KO hippocampal CA1 pyramidal neurons.
MDI-114215 reverses hippocampal LTP deficits in a mouse model of FXS, potently decreases phosphorylated cofilin levels in iPSC-derived neurons from FXS patients.
