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The potent BACE1 inhibitor LY2886721 elicits robust central Aβ pharmacodynamic responses in mice, dogs, and humans
May PC, Willis BA, Lowe SL, Dean RA, Monk SA, Cocke PJ, Audia JE, Boggs LN et al.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015-01-01
Topic: Disease mechanisms in lab and animal studies
BACE1 is a key protease controlling the formation of amyloid β, a peptide hypothesized to play a significant role in the pathogenesis of Alzheimer's disease (AD). Therefore, the development of potent and selective inhibitors of BACE1 has been a focus of many drug discovery efforts in academia and industry. Herein, we report the nonclinical and early clinical development of LY2886721, a BACE1 active site inhibitor that reached phase 2 clinical trials in AD. LY2886721 has high selectivity against key off-target proteases, which efficiently translates in vitro activity into robust in vivo amyloid β lowering in nonclinical animal models. Similar potent and persistent amyloid β lowering was observed in plasma and lumbar CSF when single and multiple doses of LY2886721 were administered to healthy human subjects. Collectively, these data add support for BACE1 inhibition as an effective means of amyloid lowering and as an attractive target for potential disease modification therapy in AD.
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APA 7th
May, P. C., Willis, B. A., Lowe, S. L., Dean, R. A., Monk, S. A., Cocke, P. J., et al. (2015). The potent BACE1 inhibitor LY2886721 elicits robust central Aβ pharmacodynamic responses in mice, dogs, and humans. The Journal of neuroscience : the official journal of the Society for Neuroscience. https://doi.org/10.1523/jneurosci.4129-14.2015
Vancouver
May PC, Willis BA, Lowe SL, Dean RA, Monk SA, Cocke PJ, et al. The potent BACE1 inhibitor LY2886721 elicits robust central Aβ pharmacodynamic responses in mice, dogs, and humans. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2015. doi:10.1523/jneurosci.4129-14.2015. PMID: 25609634.
BibTeX
@article{may2015-25609634,
author = {May, P. C. and Willis, B. A. and Lowe, S. L. and Dean, R. A. and Monk, S. A. and Cocke, P. J. and Audia, J. E. and Boggs, L. N. and others},
title = {{The potent BACE1 inhibitor LY2886721 elicits robust central Aβ pharmacodynamic responses in mice, dogs, and humans}},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
year = {2015},
doi = {10.1523/jneurosci.4129-14.2015},
pmid = {25609634},
url = {https://doi.org/10.1523/jneurosci.4129-14.2015}
}
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Key findings
- BACE1 is a key protease controlling the formation of amyloid β, a peptide hypothesized to play a significant role in the pathogenesis of Alzheimer's disease (AD).
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Study details
- Study designclinical trial
- Evidence strengthLow
How this study scored 57/100
Published in a peer-reviewed journal, and it is a randomised controlled trial. Scored zero for sample size and effect reported because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 33 of the 58 points we could judge it on, which is 57 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of neuroscience : the official journal of the Society for Neuroscience) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 11 / 12 | A randomised controlled trial (from PubMed type “Randomized Controlled Trial”) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2015 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “mice”) — scores zero |
| Randomised / blinded | 1 / 2 | Randomised (as stated in the record) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25609634) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 33 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 33 of the 58 points we could judge it on is 57 out of 100. |
| Total | 57 / 100 | — |
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