verubecestat (MK-8931) / Merck (MSD) 
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 14 Diseases   1 Trial   1 Trial   211 News 


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  • ||||||||||  verubecestat (MK-8931) / Merck (MSD)
    Journal:  The ?-Secretase 1 Enzyme as a Novel Therapeutic Target for Prostate Cancer. (Pubmed Central) -  Jan 11, 2024   
    Treatment with a pharmacological inhibitor of BACE1 (MK-8931) strongly reduced the proliferation of PCa cells in in vitro and in vivo models, analyzed by multiple assays (MTT, clonogenic, and trypan blue exclusion assays and IHC)...Furthermore, analysis of tumor tissue using the prostate cancer-specific pathway array revealed the alteration of several genes involved in PCa growth and progression including Forkhead O1 (FOXO1). All together, these findings suggest BACE1 as a novel therapeutic target in advanced PCa.
  • ||||||||||  verubecestat (MK-8931) / Merck (MSD)
    Neuropathological changes of a patient with AD treated with verubecestat (Elicium 2 (RAI Amsterdam Convention Centre)) -  Jul 6, 2023 - Abstract #AAIC2023AAIC_9014;    
    accumulation and neuritic derangement in AD. Neuropathological data could help to understand the effect of BACE inhibition in humans.
  • ||||||||||  atabecestat (JNJ-54861911) / J&J, verubecestat (MK-8931) / Merck (MSD), umibecestat (CNP520) / Novartis, Amgen, Banner Alzheimer's Institute
    Human CSF pharmacoproteomics establishes in vivo-relevant BACE1 substrates as pharmacodynamic biomarkers for chronic BACE inhibition in clinical trials (Elicium 2 (RAI Amsterdam Convention Centre)) -  Jul 6, 2023 - Abstract #AAIC2023AAIC_9013;    
    A reduction of the inhibitor dose to less than 50% BACE1 inhibition may be an appropriate strategy to avoid side effects in future clinical trials with BACE inhibitors. Our analysis also demonstrates that proteomics enables pharmacodynamic studies of multiple CSF proteins in single measurements, which are suitable for precision medicine approaches in future clinical trials with BACE inhibitors.
  • ||||||||||  verubecestat (MK-8931) / Merck (MSD), Mycamine (micafungin) / Astellas
    Preclinical, Journal:  In Silico Identification and In Vitro Validation of Repurposed Compounds Targeting the RSV Polymerase. (Pubmed Central) -  Jun 28, 2023   
    We also validated Micafungin's inhibition of the RSV RdRP using an in vitro transcription assay. These findings contribute to RSV drug development and hold promise for broad-spectrum antivirals targeting the non-segmented negative-sense (NNS) RNA viral polymerases, including those of rabies (RABV) and Ebola (EBOV).
  • ||||||||||  verubecestat (MK-8931) / Merck (MSD), lanabecestat (AZD3293) / AstraZeneca, Eli Lilly, elenbecestat (E2609) / Eisai, Biogen
    Journal:  BACE-1 Inhibitors Targeting Alzheimer's Disease. (Pubmed Central) -  Jun 13, 2023   
    The current status of developing new peptidomimetic, non-peptidomimetic, naturally occurring, and other class inhibitors are demonstrated, considering their main limitations and lessons learned. The goal is to provide a broad and complete approach to the subject, exploring new chemical classes and perspectives.
  • ||||||||||  Journal:  ?-Secretase-1: In Silico Drug Reposition for Alzheimer's Disease. (Pubmed Central) -  May 17, 2023   
    These candidates exhibit pharmacophore-specific features, including the indole or thioindole group, and interactions with key amino acids in BACE-1. Overall, this study provides insights into the potential use of in silico methods for drug repurposing and identification of new candidates for the treatment of Alzheimer's disease, especially those targeting BACE-1.
  • ||||||||||  Tazverik (tazemetostat) / Eisai, Ipsen
    PK/PD data, Preclinical, Journal:  Pharmacokinetics of Herb-Drug Interactions of Plumbagin and Tazemetostat in Rats by UPLC-MS/MS. (Pubmed Central) -  Oct 13, 2022   
    The C of tazemetostat in the experimental group was 32.48% higher than that in the control group, and the AUC and AUC of tazemetostat in the experimental group were 46.24% and 46.67% higher than that in the control group, respectively, and the t was prolonged from 10.56 h to 11.73 h. A simple, rapid and sensitive UPLC-MS/MS method for the determination of tazemetostat in rat plasma was established. PLB can inhibit the metabolism of tazemetostat and increase the plasma exposure of tazemetostat in rats.
  • ||||||||||  verubecestat (MK-8931) / Merck (MSD)
    Preclinical, Journal:  Prophylactic evaluation of verubecestat on disease- and symptom-modifying effects in 5XFAD mice. (Pubmed Central) -  Jul 20, 2022   
    At the same dose range effective at attenuating Aβ levels, verubecestat produced side effects in the absence of improvements in cognitive function. Taken together these data demonstrate the rigorous translational approaches of the MODEL-AD PTC for interrogating potential therapeutics and provide insight into the limitations of verubecestat as a prophylactic intervention for early-stage AD.
  • ||||||||||  verubecestat (MK-8931) / Merck (MSD)
    Preclinical, Journal:  An isogenic panel of App knock-in mouse models: Profiling β-secretase inhibition and endosomal abnormalities. (Pubmed Central) -  Jun 15, 2022   
    Comparison of isogenic App knock-in lines revealed that multiple factors, including elevated C-terminal fragment β (CTF-β) and humanization of Aβ might influence endosomal alterations in vivo. Thus, experimental comparisons between different isogenic App, knock-in mouse lines will provide previously unidentified insights into our understanding of the etiology of AD.
  • ||||||||||  verubecestat (MK-8931) / Merck (MSD)
    P3 data, PK/PD data, Clinical Trial,Phase III, Journal:  An Investigation of Instability in Dried Blood Spot Samples for Pharmacokinetic Sampling in Phase 3 Trials of Verubecestat. (Pubmed Central) -  Apr 13, 2022   
    P2/3, P3
    Furthermore, after increasing desiccant amounts, degradant concentrations accounted for approximately 7% of the verubecestat concentration in DBS clinical samples, indicating that issues with sample handling were minimized with new storage and shipping conditions. This case study illustrates the challenges with employing new sampling techniques in large, global trials, and the importance of anticipating and mitigating implementation risks.
  • ||||||||||  verubecestat (MK-8931) / Merck (MSD), lanabecestat (AZD3293) / AstraZeneca, Eli Lilly
    Journal:  BACE1 controls synaptic function through modulating release of synaptic vesicles. (Pubmed Central) -  Mar 15, 2022   
    Similarly, mice treated with mGluR1 PAM showed significantly mitigated synaptic deficits caused by BACE1 inhibitors. Together, our data suggest that a therapy combining BACE1 inhibitors for reducing amyloid deposition and an mGluR1 PAM for counteracting BACE1-mediated synaptic deficits appears to be an effective approach for treating AD patients.
  • ||||||||||  DEVELOPING BETA-SECRETASE INHIBITORS FOR TREATMENT OF ALZHEIMER’S DISEASE () -  Mar 9, 2022 - Abstract #ADPD2022ADPD_1122;    
    The capability of BACE1 to apply such a therapeutic candidate for AD therapy has just been examined during the previous decade. There is proof indicate that the 1 inhibitor administrating time is critical and make big difference in how successful they are in curing AD.
  • ||||||||||  verubecestat (MK-8931) / Merck (MSD), lanabecestat (AZD3293) / AstraZeneca, Eli Lilly
    Journal:  Cognitive outcomes in trials of two BACE inhibitors in Alzheimer's disease. (Pubmed Central) -  Sep 29, 2021   
    Our model explains the results of clinical trials and provides guidance for future therapeutic development. In both studies, many measures showed treatment-associated cognitive worsening, whereas verbal fluency tasks showed improvement.
  • ||||||||||  Review, Journal:  Selective Secretase Targeting for Alzheimer's Disease Therapy. (Pubmed Central) -  Sep 17, 2021   
    Such therapeutic tools shall focus on slowing down or minimizing the progression of neuronal damage. Here, we summarize structures and the activities of the latest compounds designed for AD treatment, with remarkable in vitro, in vivo, and clinical phase activities.
  • ||||||||||  verubecestat (MK-8931) / Merck (MSD), neflamapimod (VX-745) / EIP Pharma, lanabecestat (AZD3293) / AstraZeneca, Eli Lilly
    Clinical Results with Novel Approaches that Reverse BFCN Dysfunction (Ballroom) -  Aug 7, 2021 - Abstract #CTAD2021CTAD_12;    
    In the case of BACE inhibition, clinical evidence supporting the approach to target BFCN dysfunction was provided in a combined retrospective analysis of phase 3 clinical trials conducted with verubecestat and lanabecestat, respectively, in which the effects of these BACE inhibitors on specific cognitive domains were evaluated...In the case of p38α inhibition, results of a phase 2, 91-patient, 16-week, placebo-controlled study (“AscenD-LB”) with the specific p38α kinase inhibitor neflamapimod (at 40mg TID) demonstrated statistically significant, clinically relevant effect size (0.5) improvement relative to placebo in a cognitive test battery assessing attention and executive function...Finally, dose-dependent improvement relative to placebo was seen in hallucination severity and frequency, another outcome considered related to cholinergic dysfunction. The results of the AscenD-LB study, the totality of which indicates a substantial positive effect on BFCN function, are to be confirmed in a 160-patient phase 2b study that is planned to commence in the fourth quarter of 2021.
  • ||||||||||  Review, Journal:  BACE1 inhibitors: Current status and future directions in treating Alzheimer's disease. (Pubmed Central) -  Jul 9, 2021   
    Furthermore, the review demonstrates with increasing evidence that despite tremendous efforts and promising results conceived with BACE1 inhibitors, the latest studies suggest that their clinical use for treating Alzheimer's disease should be reconsidered. Finally, the review sheds light on alternative therapeutic options for targeting AD.
  • ||||||||||  verubecestat (MK-8931) / Merck (MSD)
    Journal:  BACE inhibition causes rapid, regional, and non-progressive volume reduction in Alzheimer's disease brain. (Pubmed Central) -  Mar 2, 2021   
    P2/3
    There was a moderate correlation between volumetric MRI changes and cognitive decline in all groups including placebo at Week 78 (e.g. r = -0.45 to -0.55, P < 0.001 for whole brain), but the correlations were smaller at Week 13 and significant only for the verubecestat groups (e.g. r = -0.15 and -0.11, P < 0.04 for whole brain). Our results suggest that the verubecestat-associated MRI brain volume loss is not due to generalized, progressive neurodegeneration, but may be mediated by specific effects on BACE-related amyloid processes.
  • ||||||||||  sirolimus / Generic mfg.
    [VIRTUAL] Quantitative systems pharmacology model of Alzheimers disease to study efficacy of combinatorial therapy on multiple pathology components () -  Aug 2, 2020 - Abstract #AAIC2020AAIC_3332;    
    Multiple in vitro data for intracellular dynamics perturbations (rapamycin, proteasome inhibitors, vinblastine) available from the literature were used to estimate the intracellular regulation parameters...Data from clinical studies for immunotherapy (BAN2401) and BACE inhibitor (verubecestat) have been used for retrospective model validation, together with data for treatment by rapamycin, calpain inhibitors, proteasome activation in mouse AD models... QSP modeling allows for choice of combinations of newly emerging biologics combined with targeting cell metabolism, to lead optimization and increase of treatment efficacy.