866323-14-0

ChEBI: Belinostat is a hydroxamic acid-type histone deacetylase (HDAC) inhibitor with antineoplastic activity. It has a role as an antineoplastic agent and an EC 3.5.1.98 (histone deacetylase) inhibitor. It is a hydroxamic acid, a sulfonamide and an olefinic compound.

This synthetic epigenetic modulator (FW = 318.35 g/mol; CAS 866323-14- 0), also known as PXD101 and the IUPAC name, (2E) -N-hydroxy-3-[3- (phenylsulfamoyl) phenyl]prop-2-enamide, inhibits histone deacetylase (IC50 = 27 nM) and induces a concentration-dependent increase (over the 0.2–5 μM range) in histone H4 acetylation and alters expression of genes located on DNA associated with its parent histone octamer. A simple and sensitive high-performance liquid chromatography ultraviolet method has been developed for the quantification of PXD101 in human plasma. In Rhesus monkeys, belinostat is cleared rapidly from plasma with a half-life of 1.0 h, a mean residence time of 0.47 h, and a clearance of 425 mL/min/m2 . CSF drug exposure is <1% of plasma drug exposure and <10% of free (non-protein bound) plasma drug exposure. The DNA-methylation inhibitor decitabine and histone-deacetylase inhibitor belinostat increases the efficacy of chemotherapeutic agents in tumors that acquired drug resistance due to DNA methylation and gene silencing.