LMK-235

LMK-235 is a potent and selective HDAC4/5 inhibitor, inhibits HDAC5, HDAC4, HDAC6, HDAC1, HDAC2, HDAC11 and HDAC8, with IC₅₀s of 4.22 nM, 11.9 nM, 55.7 nM, 320 nM, 881 nM, 852 nM and 1278 nM, respectively, and is used in cancer research. IC50 & Target:IC50: 4.22 nM (HDAC5), 11.9 nM (HDAC4), 55.7 nM (HDAC6), 320 nM (HDAC1), 881 nM (HDAC2), 852 nM (HDAC11), 1278 nM (HDAC8)^[1] In Vitro:LMK-235 shows cytotoxic activity against human ovarian cancer cell lines A2780 and A2780 CisR, with IC₅₀s of 0.49 μM and 0.32 μM, respectively. LMK-235 inhibits HDAC in A2780 and A2780 CisR cell lines, with IC₅₀s of 0.65 μM and 0.32 μM, respectively. LMK-235 produces a higher reduction in cell viability in comparison to the combination of cisplatin and vorinostat in all cell lines^[1]. LMK-235 (0, 0.625, 1.25, 2.5, 5, 10, and 20 μM) reduces the proliferation of BC cells in a dose- and time-dependent manner. LMK-235 (0-800 nM) also inhibits the growth of BC cells. Moreover, LMK-235 synergizes with bortezomib in BC cell lines^[2]. LMK235 (2, 20 nM) decreases in HDAC4 nuclear accumulation in Cdkl5 -/Y NPCs, completely restores the reduced number of neurons generated from Cdkl5 -/Y NPCs. LMK235 also restores histone 3 acetylation in Cdkl5 -/Y NPCs. LMK235 causes a notable increase in the isoform IV, but does not affect BDNF isoforms I or II^[3]. In Vivo:LMK235 (5 and 20 mg/kg) restores survival and maturation of postmitotic granule neurons in Cdkl5 -/Y mice. LMK235 also restores synapse development in the dentate gyrus and hippocampus of Cdkl5 -/Y mice. Furthermore, LMK235 restores hippocampus-dependent learning and memory in Cdkl5 -/Y mice^[3].