Synapsinostat

Synapsinostat
Clinical data
Other names	CN13
Drug class	Histone deacetylase inhibitor; Cognitive enhancer
ATC code	None;
Identifiers
	IUPAC name N-[(E)-(2-bromophenyl)methylideneamino]-N'-hydroxyheptanediamide;
PubChem CID	42612827;
ChemSpider	26286755;
Chemical and physical data
Formula	C14H18BrN3O3
Molar mass	356.220 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1=CC=C(C(=C1)/C=N/NC(=O)CCCCCC(=O)NO)Br;
	InChI InChI=1S/C14H18BrN3O3/c15-12-7-5-4-6-11(12)10-16-17-13(19)8-2-1-3-9-14(20)18-21/h4-7,10,21H,1-3,8-9H2,(H,17,19)(H,18,20)/b16-10+; Key:ADVRIFQAHYTQJB-MHWRWJLKSA-N;

Synapsinostat, also known as CN13, is a histone deacetylase (HDAC) inhibitor and possible cognitive enhancer.^[1]^[2]^[3] It potently inhibits the class I HDAC1, HDAC2, and HDAC3, with IC₅₀Tooltip half-maximal inhibitory concentration values of 39 nM, 41 nM, and 100 nM, respectively, whereas other HDACs were not assessed.^[2] The drug has been found to potently promote synaptogenesis in vitro.^[2]^[3] Synapsinostat was first described in the scientific literature by 2009.^[1]^[2] Subsequently, other improved analogues acting as HDAC inhibitors such as crebinostat and neurinostat, which show much greater potency, were described.^[4]

References

1 2 Patel V, Mazitschek R, Coleman B, Nguyen C, Urgaonkar S, Cortese J, et al. (April 2009). "Identification and characterization of small molecule inhibitors of a class I histone deacetylase from Plasmodium falciparum". Journal of Medicinal Chemistry. 52 (8): 2185–2187. doi:10.1021/jm801654y. PMC 2669731. PMID 19317450.
1 2 3 4 Shi P, Scott MA, Ghosh B, Wan D, Wissner-Gross Z, Mazitschek R, et al. (October 2011). "Synapse microarray identification of small molecules that enhance synaptogenesis". Nature Communications. 2 510. Bibcode:2011NatCo...2..510S. doi:10.1038/ncomms1518. PMC 3544154. PMID 22027590. Table 2 IC50 value (nM) of compounds toward specific HDACs tested in this study. [...]
1 2 Fass DM, Schroeder FA, Perlis RH, Haggarty SJ (April 2014). "Epigenetic mechanisms in mood disorders: targeting neuroplasticity". Neuroscience. 264: 112–130. doi:10.1016/j.neuroscience.2013.01.041. PMC 3830721. PMID 23376737. Using a high-throughput, microfluidics-based, synapse microarray technology, Shi and colleagues recently described the identification of novel inducers of synaptogenesis, such as the potent HDAC inhibitor named 'synapsinostat' (Shi et al., 2011). Additionally, aiming to selectively target epigenetic mechanisms involved in CREB-mediated transcription, Fass and colleagues reported on the results of a high-throughput screen that led to the identification of another highly potent, and brain penetrant HDAC inhibitor named 'crebinostat' that regulated CREB-mediated transcription, enhanced synaptogenesis, and enhanced cognition in mice as assessed using contextual fear conditioning (Fass et al., 2013).
↑ 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.

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[PatelMazitschekColeman2009-1] 1 2 Patel V, Mazitschek R, Coleman B, Nguyen C, Urgaonkar S, Cortese J, et al. (April 2009). "Identification and characterization of small molecule inhibitors of a class I histone deacetylase from Plasmodium falciparum". Journal of Medicinal Chemistry. 52 (8): 2185–2187. doi:10.1021/jm801654y. PMC 2669731. PMID 19317450.

[ShiScottGhosh2011-2] 1 2 3 4 Shi P, Scott MA, Ghosh B, Wan D, Wissner-Gross Z, Mazitschek R, et al. (October 2011). "Synapse microarray identification of small molecules that enhance synaptogenesis". Nature Communications. 2 510. Bibcode:2011NatCo...2..510S. doi:10.1038/ncomms1518. PMC 3544154. PMID 22027590. Table 2 IC50 value (nM) of compounds toward specific HDACs tested in this study. [...]

[FassSchroederPerlis2014-3] 1 2 Fass DM, Schroeder FA, Perlis RH, Haggarty SJ (April 2014). "Epigenetic mechanisms in mood disorders: targeting neuroplasticity". Neuroscience. 264: 112–130. doi:10.1016/j.neuroscience.2013.01.041. PMC 3830721. PMID 23376737. Using a high-throughput, microfluidics-based, synapse microarray technology, Shi and colleagues recently described the identification of novel inducers of synaptogenesis, such as the potent HDAC inhibitor named 'synapsinostat' (Shi et al., 2011). Additionally, aiming to selectively target epigenetic mechanisms involved in CREB-mediated transcription, Fass and colleagues reported on the results of a high-throughput screen that led to the identification of another highly potent, and brain penetrant HDAC inhibitor named 'crebinostat' that regulated CREB-mediated transcription, enhanced synaptogenesis, and enhanced cognition in mice as assessed using contextual fear conditioning (Fass et al., 2013).

[FassReisGhosh2013-4] 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.

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[3]

[4]

See also

References