Trial reportThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
The potent BACE1 inhibitor LY2886721 elicits robust central Aβ pharmacodynamic responses in mice, dogs, and humans.
Trial report in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
82 citing papers in PubMed, 199 citations in OpenAlex.
- Further analyses of the safety of verubecestat in the phase 3 EPOCH trial of mild-to-moderate Alzheimer's disease.Alzheimer's research & therapy · 2019Trial
- Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects of PF-06751979, a Potent and Selective Oral BACE1 Inhibitor: Results from Phase I Studies in Healthy Adults and Healthy Older Subjects.Journal of Alzheimer's disease : JAD · 2019Trial
- The BACE-1 inhibitor CNP520 for prevention trials in Alzheimer's disease.EMBO molecular medicine · 2018Trial
- Clinical Bioavailability of the Novel BACE1 Inhibitor Lanabecestat (AZD3293): Assessment of Tablet Formulations Versus an Oral Solution and the Impact of Gastric pH on Pharmacokinetics.Clinical pharmacology in drug development · 2018Trial
- BACE-1 inhibitors as potential drug candidates for treatment of Alzheimer's disease: a systematic review.Molecular diversity · 2026Review
- Small Molecule Therapeutics Targeting Amyloid-β in Alzheimer's Disease: Mechanisms, Clinical Progress, and Future Strategies.Experimental neurobiology · 2026Review
- Peptide-based therapeutics in the management of Alzheimer's disease (AD) and their potential to develop novel strategies.Metabolic brain disease · 2026Review
- Neuro-Dynamic Quantitative Systems Pharmacology (QSP) model describing Alzheimer's disease pathophysiology and treatment effects.NPJ systems biology and applications · 2026Article
- Review
- Post-translational modifications in alzheimer's disease: proteome dynamics and emerging therapeutic strategies.Metabolic brain disease · 2026Review
- Targeting amyloid-β in Alzheimer's disease: A critical analysis of clinical trials and their implications for drug development.Iranian journal of basic medical sciences · 2026Review
- Article
- Alleviation of Neurological Disorders by Targeting Neurodegenerative-Associated Enzymes: Natural and Synthetic Molecules.International journal of molecular sciences · 2025Review
- Traumatic brain injury causes early aggregation of beta-amyloid peptides and NOTCH3 reduction in vascular smooth muscle cells of leptomeningeal arteries.Acta neuropathologica · 2025Article
- Amyloid-beta metabolism in age-related neurocardiovascular diseases.European heart journal · 2025Review
- Bioluminescent Pseudomonas aeruginosa and Escherichia coli for whole-cell screening of antibacterial and adjuvant compounds.Scientific reports · 2024Article
- Molecular and Cellular Foundations of Aging of the Brain: Anti-aging Strategies in Alzheimer's Disease.Cellular and molecular neurobiology · 2024Review
- Article
- The Interplay of Protein Aggregation, Genetics, and Oxidative Stress in Alzheimer's Disease: Role for Natural Antioxidants and Immunotherapeutics.Antioxidants (Basel, Switzerland) · 2024Review
- Label-free detection of Aβ-42: a liquid crystal droplet approach for Alzheimer's disease diagnosis.RSC advances · 2024Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
31 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.