2-hexyl-4-Pentynoic Acid is a potent and robust inhibitor of HDAC with IC50 value of 13 μM [1].
Histone deacetylases (HDACs) are a class of enzymes that remove acetyl groups from ε-N-acetyl lysines on histones, allowing the histones to wrap the DNA more tightly. DNA expression is regulated by de-acetylation and acetylation.
2-hexyl-4-Pentynoic Acid, a valproic acid (VPA) derivatives, is a potent and robust HDACs inhibitor. In cerebellar granule cells, 2-hexyl-4-Pentynoic Acid (5 μM) significantly and dose-dependently increased acetylated histone H3 (Ac-H3) levels, and at 50-100 μM led to a maximal increase of 600-700%, compared with only a 200% increase by VPA at 100 μM. 2-hexyl-4-Pentynoic Acid also completely blocked glutamate-induced cell death at 50-100 μM. Also, 2-hexyl-4-Pentynoic Acid restored glutamate-induced neuronal loss. At 50 μM, 2-hexyl-4-Pentynoic Acid effectively increased HSP70-1a and HSP70-1b mRNA levels through HDAC inhibition [1].
Reference:
[1]. Leng Y, Marinova Z, Reis-Fernandes MA, et al. Potent neuroprotective effects of novel structural derivatives of valproic acid: potential roles of HDAC inhibition and HSP70 induction. Neurosci Lett, 2010, 476(3): 127-132.