General description | Mocetinostat is a rationally designed, orally available, Class 1-selective, small molecule, 2-aminobenzamide HDAC inhibitor with potential antineoplastic activity. |
Biochem/Physiol
Actions | Mocetinostat is a rationally designed, orally available, Class 1-selective, small molecule, 2-aminobenzamide HDAC inhibitor with potential antineoplastic activity. Mocetinostat binds to and inhibits Class 1 isoforms of HDAC, specifically HDAC 1, 2 and 3, which may result in epigenetic changes in tumor cells and so tumor cell death; although the exact mechanism has yet to be defined, tumor cell death may occur through the induction of apoptosis, differentiation, cell cycle arrest, inhibition of DNA repair, upregulation of tumor suppressors, down regulation of growth factors, oxidative stress, and autophagy, among others. Over of Class I
HDACs 1, 2 and 3 has been found in many tumors and has been correlated with a poor prognosis. Mocetinostat is a potent HDAC inhibitor with most potency for HDAC1 with IC50 of 0.15 μM in a cell-free assay, 2- to 10 fold selectivity against HDAC2, 3, and 11, and no activity to HDAC4, 5,
6, 7, and 8. |
Application | Mocetinostat has been used in trials studying the treatment of Lymphoma, Urothelial Carcinoma, Relapsed and Refractory, Myelodysplastic Syndrome, and Metastatic Leiomyosarcoma, among others. |
