HDAC2-IN-3

HDAC2-IN-3 is a selective, orally bioavailable HDAC2 inhibitor capable of crossing the blood-brain barrier, with an IC50 of 14 nM. It increases histone acetylation levels both in cells and in vivo, enhancing long-term potentiation (LTP) in the hippocampus. HDAC2-IN-3 is applicable for Alzheimer's disease research.

HDAC2:14 nM

HDAC2-IN-3 (Compound 11) increases acetylation of H4K12 in primary cortical neurons from C57B6J mouse embryos by up to 71% at concentrations ranging from 0.01-25.3 μM over 24 hours, with an IC20 of 0.259 μM. In HDAC2-KO K562 cells, HDAC2-IN-3 (0.0411-83.3 μM; overnight) exhibits low activity against HDAC1, enhancing H3K9 acetylation by only 12% compared to a positive control. Additionally, HDAC2-IN-3 (0.1-25 μM; 48 h) shows no significant cytotoxicity towards human bone marrow CD34+ progenitor cells, with an IC50 greater than 25 μM at concentrations up to 25 μM.

HDAC2-IN-3 (Compound 11) (50 mg/kg; oral administration; single dose) increases H4K12 acetylation levels in the hippocampus of APP/PS1 mice to approximately 220% of the solvent control group, confirming its in vivo inhibition of HDAC2. Additionally, daily oral doses of HDAC2-IN-3 (50 mg/kg) for 10 consecutive days significantly enhance hippocampal LTP in 6- to 7-month-old APP/PS1 mice, indicating potential benefits for learning and memory improvement.