Wikiwand AI

Entinostat

Pharmaceutical compound From Wikipedia, the free encyclopedia

Entinostat (INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name, JANTooltip Japanese Accepted Name), 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.[1][3] 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.[1] The drug is taken orally.[1]

Trade namesJingzhuda
Other namesMS-275; MS275; SNDX-275; SNDX275
Routes of
administrationOral[1]
Drug classHistone deacetylase inhibitor; HDAC1, HDAC2, and HDAC3 inhibitor; Antineoplastic agent
Quick facts Clinical data, Trade names ...
Entinostat
Clinical data
Trade namesJingzhuda
Other namesMS-275; MS275; SNDX-275; SNDX275
Routes of
administration		Oral[1]
Drug classHistone deacetylase inhibitor; HDAC1, HDAC2, and HDAC3 inhibitor; Antineoplastic agent
ATC code
Pharmacokinetic data
Elimination half-life33–150 hours[2]
Identifiers
  • (pyridin-3-yl)methyl ({4-[(2-aminophenyl)carbamoyl]phenyl}methyl)carbamate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.158.999 Edit this at Wikidata
Chemical and physical data
FormulaC21H20N4O3
Molar mass376.416 g·mol−1
3D model (JSmol)
  • C1=CC=C(C(=C1)N)NC(=O)C2=CC=C(C=C2)CNC(=O)OCC3=CN=CC=C3
  • InChI=1S/C21H20N4O3/c22-18-5-1-2-6-19(18)25-20(26)17-9-7-15(8-10-17)13-24-21(27)28-14-16-4-3-11-23-12-16/h1-12H,13-14,22H2,(H,24,27)(H,25,26) X markN
  • Key:INVTYAOGFAGBOE-UHFFFAOYSA-N X markN
 X markNcheckY (what is this?)  (verify)
Close

Medical uses

Entinostat is approved for the treatment of HER2-negative breast cancer in China.[1][3]

Side effects

Side effects of entinostat include fatigue, nausea, vomiting, anorexia, diarrhea, anemia, thrombocytopenia, neutropenia, leukopenia, hypoalbuminemia, hypophosphatemia, hyperglycemia, and hyponatremia, among others.[2]

Pharmacology

Pharmacodynamics

More information Enzyme, IC50Tooltip Half-maximal inhibitory concentration (nM) ...
Entinostat activities
EnzymeIC50Tooltip Half-maximal inhibitory concentration (nM)
HDAC1243–427
HDAC2306–753
HDAC3248–1,577
HDAC4>100,000
HDAC5>30,000
HDAC6>100,000
HDAC7>30,000
HDAC82,700–82,500
HDAC9>30,000
HDAC1094,700
HDAC11>10,000
Refs: [4][5][6][7][8]
Close

Entinostat is a benzamide histone deacetylase inhibitor.[9][10][11][12] It is a selective inhibitor of the class I HDACs, including HDAC1, HDAC2, and HDAC3, with IC50Tooltip half-maximal inhibitory concentration values of 243 to 453 nM and high selectivity over other HDACs.[4][5][6] However, it has also been reported to inhibit the class IV HDAC11,[2] though findings are mixed.[7]

Pharmacokinetics

Entinostat shows poor penetration into the brain in non-human primates.[13] The elimination half-life of entinostat is 33 to 150 hours in humans.[2]

History

Entinostat was first described in the scientific literature, under the developmental code name MS-275, in 1999.[14][15]

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.[16]

Research

Entinostat has been studied as a potential reversible male contraceptive.[17]

See also

References

Related Articles

Timelines

Top Qs

Fact Checks