β-Site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors offer the potential of disease-modifying treatment for Alzheimer's disease (AD). Since 2014, major breakthroughs have appeared in the field of BACE1 inhibitors. This review provides an overview of amidine-based BACE1 inhibitors between 2014 and 2018. Herein are summarized i) the structure-activity relationship, ii) the physiological results and iii) the potential risks from a lack of selectivity. This review also summarizes clinical scope, results and outlook of the compounds that have been or are currently under development in clinical trials.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.bmcl.2018.12.049 | DOI Listing |
Brain Sci
November 2024
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia.
Background/objectives: Diabetes mellitus (DM), a widespread endocrine disorder characterized by chronic hyperglycemia, can cause nerve damage and increase the risk of neurodegenerative diseases such as Alzheimer's disease (AD). Effective blood glucose management is essential, and sitagliptin (SITG), a dipeptidyl peptidase-4 () inhibitor, may offer neuroprotective benefits in type 2 diabetes mellitus (T2DM).
Methods: T2DM was induced in rats using nicotinamide (NICO) and streptozotocin (STZ), and biomarkers of AD and DM-linked enzymes, inflammation, oxidative stress, and apoptosis were evaluated in the brain.
Curr Alzheimer Res
December 2024
Silicon Script Sciences Private Limited, Bharatpur, Gorahi-22400, Dang, Nepal.
Background: Alzheimer's disease (AD) is marked by cognitive decline, amyloid plaques, neurofibrillary tangles, and cholinergic loss. Due to the limited success of amyloid-targeted therapies, attention has shifted to new non-amyloid targets like phosphodiesterases (PDE). This study investigates the potential of Flemingia vestita (FV) phytomolecules and derivatives, particularly 8-Prenyldaidzein, in AD treatment.
View Article and Find Full Text PDFFront Pharmacol
December 2024
Department of Health and Pharmaceutical Sciences, Faculty of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, Madrid, Spain.
Alzheimer's disease (AD) is a major neurodegenerative disorder that courses with chronic neuroinflammation. Pleiotrophin (PTN) is an endogenous inhibitor of Receptor Protein Tyrosine Phosphatase (RPTP) β/ζ which is upregulated in different neuroinflammatory disorders of diverse origin, including AD. To investigate the role of RPTPβ/ζ in neuroinflammation and neurodegeneration, we used eight-to ten-month-old APP/PS1 AD mouse model.
View Article and Find Full Text PDFSAR QSAR Environ Res
December 2024
Department of Pharmacognosy, Faculty of Pharmacognosy and Traditional Medicine, Hanoi University of Pharmacy, Hanoi, Vietnam.
A comprehensive computational strategy that combined QSAR modelling, molecular docking, and ADMET analysis was used to discover potential inhibitors for β-secretase 1 (BACE-1). A dataset of 1,138 compounds with established BACE-1 inhibitory activities was used to build a QSAR model using mol2vec descriptors and support vector regression. The obtained model demonstrated strong predictive performance (training set: = 0.
View Article and Find Full Text PDFACS Nano
January 2025
Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau SAR 999078, China.
More than the sparse infiltration in glioblastoma, cytotoxic T lymphocytes (CTLs) also function inefficiently and overexpress the inhibitory markers, especially the identified NK cell receptor (NK1.1). However, most studies solely focus on how to augment tumor-infiltrating CTLs and overlook their killing maintenance.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!