Clinical data | |
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Other names | BNN20; 17β-Spiro-(androst-5-en-17,2'-oxiran)-3β-ol |
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CAS Number | |
PubChem CID | |
ChemSpider | |
UNII | |
ChEMBL | |
Chemical and physical data | |
Formula | C20H30O2 |
Molar mass | 302.458 g·mol−1 |
3D model ( JSmol) | |
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BNN-20, also known as 17β-spiro-(androst-5-en-17,2'-oxiran)-3β-ol, is a synthetic neurosteroid, " microneurotrophin", and analogue of the endogenous neurosteroid dehydroepiandrosterone (DHEA). [1] [2] It acts as a selective, high- affinity, centrally active agonist of the TrkA, TrkB, and p75NTR, receptors for the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), as well as for DHEA and DHEA sulfate (DHEA-S). [2] [3] The drug has been suggested as a potential novel treatment for Parkinson's disease and other conditions. [2]
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. [3] 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. [4] 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). [3] [4] In any case, DHEA and DHEA-S were identified as important endogenous neurotrophic factors. [3] These findings may explain the positive association between decreased circulating DHEA levels with age and age-related neurodegenerative diseases. [2]
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] Of these, BNN-20 was assayed and found to directly bind to and activate the TrkA, TrkB, and p75NTR. [2] In addition, it was found to cross the blood–brain barrier and to have strong neuroprotective effects on dopaminergic neurons in vivo in a mouse model of dopaminergic neurodegeneration, which were dependent, at least in part, on activation of the TrkB. [2] Moreover, unlike DHEA, it lacked any hormonal actions. [2] As such, BNN-20 was described as a BDNF mimetic and was proposed as a potential novel treatment for Parkinson's disease and other conditions, particularly of the neurodegenerative variety, like amyotrophic lateral sclerosis. [2] [5]
Clinical data | |
---|---|
Other names | BNN20; 17β-Spiro-(androst-5-en-17,2'-oxiran)-3β-ol |
Identifiers | |
| |
CAS Number | |
PubChem CID | |
ChemSpider | |
UNII | |
ChEMBL | |
Chemical and physical data | |
Formula | C20H30O2 |
Molar mass | 302.458 g·mol−1 |
3D model ( JSmol) | |
| |
|
BNN-20, also known as 17β-spiro-(androst-5-en-17,2'-oxiran)-3β-ol, is a synthetic neurosteroid, " microneurotrophin", and analogue of the endogenous neurosteroid dehydroepiandrosterone (DHEA). [1] [2] It acts as a selective, high- affinity, centrally active agonist of the TrkA, TrkB, and p75NTR, receptors for the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), as well as for DHEA and DHEA sulfate (DHEA-S). [2] [3] The drug has been suggested as a potential novel treatment for Parkinson's disease and other conditions. [2]
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. [3] 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. [4] 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). [3] [4] In any case, DHEA and DHEA-S were identified as important endogenous neurotrophic factors. [3] These findings may explain the positive association between decreased circulating DHEA levels with age and age-related neurodegenerative diseases. [2]
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] Of these, BNN-20 was assayed and found to directly bind to and activate the TrkA, TrkB, and p75NTR. [2] In addition, it was found to cross the blood–brain barrier and to have strong neuroprotective effects on dopaminergic neurons in vivo in a mouse model of dopaminergic neurodegeneration, which were dependent, at least in part, on activation of the TrkB. [2] Moreover, unlike DHEA, it lacked any hormonal actions. [2] As such, BNN-20 was described as a BDNF mimetic and was proposed as a potential novel treatment for Parkinson's disease and other conditions, particularly of the neurodegenerative variety, like amyotrophic lateral sclerosis. [2] [5]