AZD3839 / AstraZeneca - LARVOL DELTA

Shedding new light on BACE1-mediated modulation of IL-6 signaling: Implications for neural activity and synaptic plasticity in mice. (PubMed, Cytokine) - "Interestingly, a dramatic rebound effect on excitatory postsynaptic potentials was observed with BACE1 inhibitor AZD3839 but not verubecestat during wash out. Our results support relevant and differential roles of IL-6, LIF and BACE1 in pathways modulating neuronal discharge activity in the cerebellum and the synaptic plasticity in the hippocampus, and a possible involvement of this interaction in deficits of memory and learning."

Journal • Preclinical • IL6 • IL6R

Insilico targeting of virus entry facilitator NRP1 to block SARS-CoV2 entry. (PubMed, PLoS One) - "Computational modeling of the interaction between the b1 domain of NRP1 and the receptor-binding domain of the spike protein suggested that AZD3839 and LY2090314 could effectively hinder the NRP1-spike interaction. Therefore, these compounds may serve as potential drug candidates to reduce SARS-CoV-2 infectivity."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • NRP1

Fragment-Based Drug Discovery by NMR. Where Are the Successes and Where can It Be Improved? (PubMed, Front Mol Biosci) - "More precisely, we examine the development history from the primary screening to the final lead optimisation of AZD3839 interacting with BACE-1, ABT-199 interacting with BCL and S64315 interacting with MCL-1. Based on these studies, we derive observations and conclusions regarding the FBDD process by NMR and discuss its potential improvements."

Journal • MCL1

NEW CELLULAR MODELS TO STUDY ALZHEIMER'S DISEASE USING CRISPR/CAS9 TECHNOLOGY (ADPD 2017) - "...Treatment of PSEN1M146V mutant cells with the beta-secretase inhibitor AZD3839 significantly reduced the secretion of both Ab42 and Ab40 while Ab42/Ab40 ratio remained high at all the concentrations tested...Cells endogenously expressing fAD mutations are a valuable tool for the evaluation of drugs and key aspects of AD pathogenesis."

Preclinical • Alzheimer's Disease • Biosimilar • CNS Disorders • Parkinson's Disease

A series of molecular modeling techniques to reveal selective mechanisms of inhibitors to β-Site amyloid precursor protein cleaving enzyme 1 (BACE1) and β-Site amyloid precursor protein cleaving enzyme 2 (BACE2). (PubMed, J Biomol Struct Dyn) - "Recently, it has been reported that a potential BACE1 inhibitor named C28 (∼52-fold selectivity) exhibited greater selectivity to BACE1 over BACE2 than the previously reported inhibitors AZD3293 and AZD3839 (∼1.5-fold and 14-fold selectivity). In addition, the umbrella sampling simulations revealed the inhibitors' different patterns of dissociation from the binding pockets of BACE1 and BACE2, and that different energy barriers were responsible for the selectivity. The physical principles revealed by this study may facilitate the rational design of more potent BACE1 selective inhibitors."

Journal