Bnn-27

BNN-27
Clinical data
Other names	BNN27; (20R)-3β,21-Dihydroxy-17α,20-epoxypregn-5-ene; 17α,20R-Epoxypregn-5-ene-3β,21-diol
Identifiers
	IUPAC name (3S,8R,9S,10R,13S,14S,17R)-3'-(Hydroxymethyl)-10,13-dimethylspiro[1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthrene-17,2'-oxirane]-3-ol;
PubChem CID	25154755;
ChemSpider	24660621;
Chemical and physical data
Formula	C21H32O3
Molar mass	332.484 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C[C@]12CC[C@@H](CC1=CC[C@@H]3[C@@H]2CC[C@]4([C@H]3CC[C@]45C(O5)CO)C)O;
	InChI InChI=1S/C21H32O3/c1-19-8-5-14(23)11-13(19)3-4-15-16(19)6-9-20(2)17(15)7-10-21(20)18(12-22)24-21/h3,14-18,22-23H,4-12H2,1-2H3/t14-,15+,16-,17-,18?,19-,20-,21-/m0/s1; Key:FMOHTQBFGJULLE-HNFJNZPISA-N;

Short description: Chemical compound

BNN-27, also known as 17α,20R-epoxypregn-5-ene-3β,21-diol, is a synthetic neurosteroid and "microneurotrophin" and analogue of the endogenous neurosteroid dehydroepiandrosterone (DHEA).^[1]^[2]^[3]^[4] It acts as a selective, high-affinity, centrally active agonist of the TrkA and p75^NTR, receptors for nerve growth factor (NGF) and other neurotrophins, as well as for DHEA and DHEA sulfate (DHEA-S).^[2]^[3]^[5] BNN-27 has neuroprotective and neurogenic effects and has been suggested as a potential novel treatment for neurodegenerative diseases and brain trauma.^[2]^[3]

In 2011, the surprising discovery was made that DHEA, as well as DHEA-S, directly bind to and activate the TrkA and p75^NTR with high affinity.^[5] DHEA was subsequently also found to bind to the TrkB and TrkC with high affinity, though it notably activated the TrkC but not the TrkB.^[6] DHEA and DHEA-S bound to these receptors with affinities that were in the low nanomolar range (around 5 nM), although the affinities were nonetheless approximately two orders of magnitude lower relative to the highly potent polypeptide neurotrophins (0.01–0.1 nM).^[5]^[6] In any case, DHEA and DHEA-S were identified as important endogenous neurotrophic factors.^[5] These findings may explain the positive association between decreased circulating DHEA levels with age and age-related neurodegenerative diseases.^[5]

Subsequently, a series of spiro derivatives of DHEA that had been synthesized and assessed in 2009 as potential neuroprotective agents was re-investigated.^[1]^[2]^[3] Of these, BNN-27 was assayed and found to directly bind to and activate the TrkA and p75^NTR.^[2]^[3] In addition, it was found to cross the blood–brain barrier and to have strong neuroprotective and neurogenic effects in mouse models of neurotoxicity and neurodegeneration.^[2]^[3] Moreover, unlike DHEA, it lacked any hormonal actions.^[2]^[3] Also, it was found to lack the problematic hyperalgesic actions of NGF.^[2]^[3] As such, BNN-27 has been described as an NGF mimetic and was proposed as a potential novel treatment for neurodegenerative diseases and brain trauma.^[2]^[3]

References

↑ ^1.0 ^1.1 "Novel dehydroepiandrosterone derivatives with antiapoptotic, neuroprotective activity". J. Med. Chem. 52 (21): 6569–87. 2009. doi:10.1021/jm900468p. PMID 19845386.
↑ ^2.0 ^2.1 ^2.2 ^2.3 ^2.4 ^2.5 ^2.6 ^2.7 ^2.8 "Selective and differential interactions of BNN27, a novel C17-spiroepoxy steroid derivative, with TrkA receptors, regulating neuronal survival and differentiation". Neuropharmacology 111: 266–282. 2016. doi:10.1016/j.neuropharm.2016.09.007. PMID 27618740. https://zenodo.org/record/895789.
↑ ^3.0 ^3.1 ^3.2 ^3.3 ^3.4 ^3.5 ^3.6 ^3.7 ^3.8 "BNN27, a 17-Spiroepoxy Steroid Derivative, Interacts With and Activates p75 Neurotrophin Receptor, Rescuing Cerebellar Granule Neurons from Apoptosis". Front Pharmacol 7: 512. 2016. doi:10.3389/fphar.2016.00512. PMID 28082899.
↑ "The novel dehydroepiandrosterone (DHEA) derivative BNN27 counteracts delay-dependent and scopolamine-induced recognition memory deficits in rats". Neurobiol Learn Mem 140: 145–153. 2017. doi:10.1016/j.nlm.2017.03.004. PMID 28274826.
↑ ^5.0 ^5.1 ^5.2 ^5.3 ^5.4 "Neurosteroid dehydroepiandrosterone interacts with nerve growth factor (NGF) receptors, preventing neuronal apoptosis". PLOS Biol. 9 (4): e1001051. 2011. doi:10.1371/journal.pbio.1001051. PMID 21541365.
↑ ^6.0 ^6.1 "Dehydroepiandrosterone: an ancestral ligand of neurotrophin receptors". Endocrinology 156 (1): 16–23. 2015. doi:10.1210/en.2014-1596. PMID 25330101. https://zenodo.org/record/894291.

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[pmid19845386-1] 1.0 ^1.1 "Novel dehydroepiandrosterone derivatives with antiapoptotic, neuroprotective activity". J. Med. Chem. 52 (21): 6569–87. 2009. doi:10.1021/jm900468p. PMID 19845386.

[pmid27618740-2] 2.0 ^2.1 ^2.2 ^2.3 ^2.4 ^2.5 ^2.6 ^2.7 ^2.8 "Selective and differential interactions of BNN27, a novel C17-spiroepoxy steroid derivative, with TrkA receptors, regulating neuronal survival and differentiation". Neuropharmacology 111: 266–282. 2016. doi:10.1016/j.neuropharm.2016.09.007. PMID 27618740. https://zenodo.org/record/895789.

[pmid28082899-3] 3.0 ^3.1 ^3.2 ^3.3 ^3.4 ^3.5 ^3.6 ^3.7 ^3.8 "BNN27, a 17-Spiroepoxy Steroid Derivative, Interacts With and Activates p75 Neurotrophin Receptor, Rescuing Cerebellar Granule Neurons from Apoptosis". Front Pharmacol 7: 512. 2016. doi:10.3389/fphar.2016.00512. PMID 28082899.

[pmid28274826-4] "The novel dehydroepiandrosterone (DHEA) derivative BNN27 counteracts delay-dependent and scopolamine-induced recognition memory deficits in rats". Neurobiol Learn Mem 140: 145–153. 2017. doi:10.1016/j.nlm.2017.03.004. PMID 28274826.

[pmid21541365-5] 5.0 ^5.1 ^5.2 ^5.3 ^5.4 "Neurosteroid dehydroepiandrosterone interacts with nerve growth factor (NGF) receptors, preventing neuronal apoptosis". PLOS Biol. 9 (4): e1001051. 2011. doi:10.1371/journal.pbio.1001051. PMID 21541365.

[pmid25330101-6] 6.0 ^6.1 "Dehydroepiandrosterone: an ancestral ligand of neurotrophin receptors". Endocrinology 156 (1): 16–23. 2015. doi:10.1210/en.2014-1596. PMID 25330101. https://zenodo.org/record/894291.

Bnn-27

See also

References