Entinostat

Structural formula
General
Non-proprietary name	Entinostat
other names	(Pyridin-3-yl) methyl [{4 - [(2-aminophenyl) carbamoyl] phenyl} methyl) carbamate; MS-275; SNDX-275;
Molecular formula	C 21 H 20 N 4 O 3
External identifiers / databases
EC number	630-693-0
ECHA InfoCard	100.158.999
PubChem	4261
ChemSpider	4111
DrugBank	DB11841
Wikidata	Q1281020
Drug information
Drug class	Cytostatic
Mechanism of action	HDAC1 & 3
properties
Molar mass	376.4 g · mol -1
safety instructions
H and P phrases	H: 301-315-319-335-360
	P: ?
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Entinostat is an experimental drug from the group of HDAC inhibitors . It has a particular affinity for two class I histone deacetylases (HDAC) , namely HDAC 1 and 3, and should therefore be used as a cytostatic agent . Entinostat is being developed by the pharmaceutical company Syndax and is in phase 2 of the clinical trial .

pharmacology

Histone deacetylases (HDACs) are enzymes , the gene expression through deacetylation of lysine residues in histone regulate and are inhibited by Entinostat. This leads to an increased presence of acetylated lysine residues, which no longer have a positive charge and can no longer interact with the negatively charged DNA . The chromatin structure relaxes .

The relaxed chromatin structure enables DNA- binding proteins , such as transcription factors , to access the DNA. This leads to easier gene expression . When therapy with entinostat two objectives:

Interfering with the expression of genes that play a role in regulating the cell cycle . B. influences cell differentiation or apoptosis .
Sensitization (medicine) of the tumors to cytostatics , therefore Entinostat should be used as a combination preparation with cytostatics or radiation therapy.

Entinostat has a wide spectrum of activity; it is said 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 .

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

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S. Park, S. Lee, B. Kim, E. Cho, S. Patel, H. Kang, E. Sausville, O. Nakanishi, J. Trepel, B. Lee, S. Kim: Transcriptional Regulation of the Transforming Growth Factor β Type II Receptor Gene by Histone Acetyltransferase and Deacetylase is Mediated by NF-Y in Human Breast Cancer Cells . The Journal of Biological Chemistry (7), 5168-5174, 2002

↑ Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A labeling of (pyridin-3-yl) methyl 4- (2-aminophenylcarbamoyl) benzylcarbamate in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on January 21, 2020, is reproduced from a self-classification by the distributor .