Crebinostat
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| Drug class | Histone deacetylase inhibitor; Cognitive enhancer |
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| Formula | C20H23N3O3 |
| Molar mass | 353.422 g·mol−1 |
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Crebinostat is a histone deacetylase (HDAC) inhibitor and possible cognitive enhancer.[1][2][3]
| 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 |
It specifically inhibits 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]
The chemical synthesis of crebinostat has been described.[1][4][5]
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
[edit]References
[edit]- 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.
- 1 2 3 4 5 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.
- 1 2 Dama D, Sharma SK (May 2024). "Crebinostat facilitates memory formation". Biochemical and Biophysical Research Communications. 710 149872. doi:10.1016/j.bbrc.2024.149872. PMID 38593621.
- ↑ 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.
- ↑ Mao Y, Zhu C, Zhu G, Wang H, Ren X (11 March 2016). "Kilogram Synthesis of Crebinostat". Synthesis. 48 (09): 1318–1321. doi:10.1055/s-0035-1561917. ISSN 0039-7881.