Crebinostat

Crebinostat is a novel cognitive enhancer that inhibits class I HDAC/1/2/3 (IC50=0.7/1.0/2.0 nM), class IIb HDAC6 (IC50=9.3 nM) with weaker inhibition of the class I HDAC8 and no significant inhibition of the class IIa HDAC/4/5/7/9; potently induces acetylation of both histone H3 and histone H4 as well as enhanced the expression of the CREB target gene Egr1 in cultured mouse primary neurons; upregulates Bdnf and Grn, and downregulates Mapt (tau) gene expression-genes; brain penetrant. (In Vitro) :Crebinostat (1 μM; 24 h) induces acetylation of AcH4K12 and AcH3K9 in mouse primary neuronal cells.Crebinostat (1 μM; 24 h) downregulates Mapt mRNA expression, and upregulates Hspa1b (Hsp70) and Bdnf mRNA expression in mouse primary cultured neurons.Crebinostat (1 μM; 24 h) increases histone acetylation and synapsin I punctae along dendrites in primary cultured neurons. (In Vivo) :Crebinostat (25 mg/kg; IP; for 10 days) enhances memory of contextual fear conditioning in mice; induces an increase in total hippocampal acetylation of H4K12 and H3K9.