Entinostat

• (Pyridin- 3-yl ) methyl ( {4 - [(2- aminophenyl ) carbamoyl ] phenyl } methyl ) carbamate
• MS -275
• SNDX -275

Cytostatic

HDAC1 & 3

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Entinostat is a class 1 HDAC inhibitor, with a special affinity for HDAC1 and 3 and should therefore be used as a cytostatic agent. Right now Entinostat in Phase 2 Clinical Trial and is developed by the pharmaceutical company Syndax.

Pharmacology

Mechanism of Action

HDAC enzymes, which are inhibited by the 2 -amino group of Entinostat that regulate gene expression through deacetylation of lysine residues in histone. By inhibition of HDAC enzymes, it is in the increased presence of acetylated lysine residues, which do not have more positive charge and no longer able to interact with the negatively charged DNA. This leads to a relaxation of chromatin structure.

Relaxing the chromatin structure allows DNA-binding proteins such as transcription factors access to the DNA. This leads to a facilitated gene expression. In the therapy with Entinostat two objectives:

The spectrum of activity of Entinostat is large, it is to be used against breast cancer, lung cancer, colon cancer, blood cancer, and pancreatic cancer. In addition Entinostat shows a selectivity towards tumor cells and so far no serious side effects.

Properties

Entinostat is to be administered orally and has a very long plasma half-life of 45-100 hours, so rich one to two doses per week.