BNN-27
Chemical compound
From Wikipedia, the free encyclopedia
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 p75NTR, 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]
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| Other names | BNN27; (20R)-3β,21-Dihydroxy-17α,20-epoxypregn-5-ene; 17α,20R-Epoxypregn-5-ene-3β,21-diol |
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| Formula | C21H32O3 |
| Molar mass | 332.484 g·mol−1 |
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In 2011, the surprising discovery was made that DHEA, as well as DHEA-S, directly bind to and activate the TrkA and p75NTR 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 p75NTR.[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]