Entinostat (, , ), sold under the brand name Jingzhuda and also known by its developmental code names SNDX-275 and MS-275, is a histone deacetylase (HDAC) inhibitor which is used in the treatment of HER2-negative breast cancer. It is also under development for the treatment of HER2-positive breast cancer and was previously under development for a large number of other cancers. The drug is taken orally.
Medical uses Entinostat is approved for the treatment of HER2-negative breast cancer in China.
Side effects Side effects of entinostat include fatigue, nausea, vomiting, anorexia, diarrhea, anemia, thrombocytopenia, neutropenia, leukopenia, hypoalbuminemia, hypophosphatemia, hyperglycemia, and hyponatremia, among others.
Pharmacology Pharmacodynamics + Enzyme (nM) HDAC1 243–427 HDAC2 306–753 HDAC3 248–1,577 HDAC4 >100,000 HDAC5 >30,000 HDAC6 >100,000 HDAC7 >30,000 HDAC8 2,700–82,500 HDAC9 >30,000 HDAC10 94,700 HDAC11 >10,000 Refs:
Entinostat is a benzamide histone deacetylase inhibitor. It is a selective inhibitor of the class I HDACs, including HDAC1, HDAC2, and HDAC3, with values of 243 to 453nM and high selectivity over other HDACs. However, it has also been reported to inhibit the class IV HDAC11, though findings are mixed.
Pharmacokinetics Entinostat shows poor penetration into the brain in non-human primates. The elimination half-life of entinostat is 33 to 150hours in humans.
History Entinostat was first described in the scientific literature, under the developmental code name MS-275, in 1999.
Syndax Pharmaceuticals held the rights to entinostat and received $26.6 million in funds to advance treatments of resistant cancers using epigenetic tools in 2016.
Research Entinostat has been studied as a potential reversible male contraceptive.
See also Histone deacetylase inhibitor
References