Chemistry:Crebinostat
Crebinostat is a histone deacetylase (HDAC) inhibitor and possible cognitive enhancer.[1][2][3]
Pharmacology
| Enzyme | IC50 (nM) |
|---|---|
| HDAC1 | 0.7–1.4 |
| HDAC2 | 1.0–2.1 |
| HDAC3 | 2.0–3.4 |
| HDAC4 | >2,000 |
| HDAC5 | >2,000 |
| HDAC6 | 0.6–9.3 |
| HDAC7 | >2,000 |
| HDAC8 | >2,000 |
| HDAC9 | >2,000 |
| HDAC10 | ND |
| HDAC11 | ND |
| Refs: [1][2] | |
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.[1][2] The drug has been found to robustly activate CREB-mediated transcription and to upregulate brain-derived neurotrophic factor (BDNF) expression and increase synaptogenesis.[1] It has been found to enhance memory in rodents.[1][3] The pharmacokinetics of crebinostat have been studied in rodents.[1]
Chemistry
The chemical synthesis of crebinostat has been described.[1][4][5] A notable analogue of crebinostat is neurinostat.[2]
History
Crebinostat was first described in the scientific literature by 2013.[1] It was identified via screening of a library of over 1,200 compounds designed to target HDACs.[1] There is interest in crebinostat as a potential novel cognitive enhancer in humans.[1][2] Subsequent to the development of crebinostat, an analogue known as neurinostat with improved properties was discovered and described.[2]
See also
- Histone deacetylase inhibitor
- Synapsinostat
- Neurinostat
- Vorinostat
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 "Crebinostat: a novel cognitive enhancer that inhibits histone deacetylase activity and modulates chromatin-mediated neuroplasticity". Neuropharmacology 64: 81–96. January 2013. doi:10.1016/j.neuropharm.2012.06.043. PMID 22771460.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 "Dissecting structure-activity-relationships of crebinostat: Brain penetrant HDAC inhibitors for neuroepigenetic regulation". Bioorganic & Medicinal Chemistry Letters 26 (4): 1265–1271. February 2016. doi:10.1016/j.bmcl.2016.01.022. PMID 26804233.
- ↑ 3.0 3.1 "Crebinostat facilitates memory formation". Biochemical and Biophysical Research Communications 710. May 2024. doi:10.1016/j.bbrc.2024.149872. PMID 38593621. Bibcode: 2024BBRC..71049872D.
- ↑ "A New and Economic Synthesis of Crebinostat". Organic Preparations and Procedures International 50 (5): 517–521. 3 September 2018. doi:10.1080/00304948.2018.1526033. ISSN 0030-4948.
- ↑ "Kilogram Synthesis of Crebinostat". Synthesis 48 (9): 1318–1321. 11 March 2016. doi:10.1055/s-0035-1561917. ISSN 0039-7881.
 |  |
