Crebinostat

Crebinostat
Clinical data
Drug classHistone deacetylase inhibitor; Cognitive enhancer
ATC code
  • None
Identifiers
  • N'-hydroxy-N-[(E)-(4-phenylphenyl)methylideneamino]heptanediamide
CAS Number
PubChem CID
ChemSpider
ChEBI
ChEMBL
Chemical and physical data
FormulaC20H23N3O3
Molar mass353.422 g·mol−1
3D model (JSmol)
  • C1=CC=C(C=C1)C2=CC=C(C=C2)/C=N/NC(=O)CCCCCC(=O)NO
  • InChI=1S/C20H23N3O3/c24-19(9-5-2-6-10-20(25)23-26)22-21-15-16-11-13-18(14-12-16)17-7-3-1-4-8-17/h1,3-4,7-8,11-15,26H,2,5-6,9-10H2,(H,22,24)(H,23,25)/b21-15+
  • Key:AEIVDBATQVVQFS-RCCKNPSSSA-N

Crebinostat is a histone deacetylase (HDAC) inhibitor and possible cognitive enhancer.

Pharmacology

Crebinostat activities
EnzymeIC50Tooltip Half-maximal inhibitory concentration (nM)
HDAC10.7–1.4
HDAC21.0–2.1
HDAC32.0–3.4
HDAC4>2,000
HDAC5>2,000
HDAC60.6–9.3
HDAC7>2,000
HDAC8>2,000
HDAC9>2,000
HDAC10ND
HDAC11ND
Refs:

Crebinostat is a histone deacetylase (HDAC) inhibitor, specifically inhibiting the class I HDAC1, HDAC2, and HDAC3, the class IIb HDAC6, and weakly the class I HDAC8, with no significant inhibition of the class IIa HDAC4, HDAC5, HDAC7, or HDAC9. The drug has been found to robustly activate CREB-mediated transcription and to upregulate brain-derived neurotrophic factor (BDNF) expression and increase synaptogenesis. It has been found to enhance memory in rodents. The pharmacokinetics of crebinostat have been studied in rodents.

Chemistry

The chemical synthesis of crebinostat has been described. A notable analogue of crebinostat is neurinostat.

History

Crebinostat was first described in the scientific literature by 2013. It was identified via screening of a library of over 1,200 compounds designed to target HDACs. There is interest in crebinostat as a potential novel cognitive enhancer in humans. Subsequent to the development of crebinostat, an analogue known as neurinostat with improved properties was discovered and described.

See also

References

  1. 1 2 3 4 5 6 7 8 9 10 Fass DM, Reis SA, Ghosh B, Hennig KM, Joseph NF, Zhao WN, et al. (January 2013). "Crebinostat: a novel cognitive enhancer that inhibits histone deacetylase activity and modulates chromatin-mediated neuroplasticity". Neuropharmacology. 64: 81–96. doi:10.1016/j.neuropharm.2012.06.043. PMC 3447535. PMID 22771460.
  2. 1 2 3 4 5 6 Ghosh B, Zhao WN, Reis SA, Patnaik D, Fass DM, Tsai LH, et al. (February 2016). "Dissecting structure-activity-relationships of crebinostat: Brain penetrant HDAC inhibitors for neuroepigenetic regulation". Bioorganic & Medicinal Chemistry Letters. 26 (4): 1265–1271. doi:10.1016/j.bmcl.2016.01.022. PMC 4753070. PMID 26804233.
  3. 1 2 Dama D, Sharma SK (May 2024). "Crebinostat facilitates memory formation". Biochemical and Biophysical Research Communications. 710 149872. Bibcode:2024BBRC..71049872D. doi:10.1016/j.bbrc.2024.149872. PMID 38593621.
  4. ↑ Zhang J, Tang Y, Liu Y, Mao Y (3 September 2018). "A New and Economic Synthesis of Crebinostat". Organic Preparations and Procedures International. 50 (5): 517–521. doi:10.1080/00304948.2018.1526033. ISSN 0030-4948.
  5. ↑ Mao Y, Zhu C, Zhu G, Wang H, Ren X (11 March 2016). "Kilogram Synthesis of Crebinostat". Synthesis. 48 (9): 1318–1321. doi:10.1055/s-0035-1561917. ISSN 0039-7881.