HDAC (Histone deacetylases) are a class of enzymes that remove acetyl groups from an ε-N-acetyl lysine amino acid on a histone. To date, There are 18 human HDACs. Besides, HDACs include four classes on the basis of their homology with yeast proteins. Class I HDACs (HDAC1, 2, 3, and 8) share high homology with the yeast transcriptional regulator RPD3. And class II HDACs are closely related to HDA1 (HDAC4, 5, 6, 7, 9, and 10). Class III HDACs, called sirtuins, are homologous with Sir2 (SIRT1, 2, 3, 4, 5, 6, and 7). And class IV HDAC (HDAC11) is homologous with class I and II enzymes. Class II HDACs include class IIa (HDAC4, 5, 7, 9) and class IIb (HDAC6 and 10) forms.
Class I, II, and VI HDACs are also referred to as “classical” HDACs and are Zn2+‐dependent enzymes whereas sirtuins require NAD+ as a cofactor. We will introduce a potent HDAC inhibitor, Abexinostat.
Lysine acetylation is a reversible modification controlled by the antagonistic actions of two types of enzymes, histone acetylases (HATs) and HDACs. Specifically, HATs catalyze the transfer of acetyl groups from acetyl CoA to the ϵ‐amino group of the lysine residue. Conversely, HDACs promote the removal of the acetyl group from the acetylated residue, releasing an acetate molecule. HDACs have emerged as crucial transcriptional co‐repressors in highly diverse physiological and pathological systems. Therefore, HDAC inhibitors constitute a new group of epigenetic agents that has gained much attention in cancer drug development.
Abexinostat acts as a potent and orally active pan-HDAC inhibitor mostly targeting HDAC1.
Abexinostat, also known as PCI-24781 or CRA-024781, is a novel, broad-spectrum hydroxamic acid-based inhibitor of HDAC. Importantly, Abexinostat causes changes to chromatin structure and to gene expression patterns, which results in the inhibition of the proliferation of cancer cells, and induction of apoptosis. What’s more, Abexinostat exhibits potent antitumor activity against a variety of tumor cell lines. Meanwhile, Abexinostat also has an antiproliferative effect on HUVEC endothelial cells. Abexinostat has potential for the research of Sarcoma, Lymphoma, Leukemia, Lymphocytic, and Hodgkin Disease, among others.
All in all, Abexinostat is a potent and broad-spectrum inhibitor of HDAC.
Reference:
[1]. Beumer JH, et, al. Curr Clin Pharmacol. 2010 Aug;5(3):196-208.