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Compound class: Synthetic organic
Comment: This compound was developed using structure-based optimization, as an antidote for acetylcholinesterase (AChE) inhibition by organophosphorus nerve agents . The mechanism of enzyme reactivation depends on antidote-induced displacement of the phosphyl group from AChE's active-site serine. The main goal of the optimization campaign was to design an AChE reactivator with improved efficacy and brain penetrance compared to existing antidotes. In in vitro AChE reactivation assays, reactivator 2 outperformed the reference reactivators 2-PAM, HI-6, and obidoxime for AChE inhibited by various organophosphate nerve agents (VX, a sarin surrogate, tabun and ethyl papaoxon). Kinetic measurements and structural studies have confirmed the potential efficacy of reactivator 2 but it has not yet been evaluated in vivo.
Ligand Activity Visualisation Charts
These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.✖
1. Santoni G, de Sousa J, de la Mora E, Dias J, Jean L, Sussman JL, Silman I, Renard PY, Brown RCD, Weik M et al.. (2018)
Structure-Based Optimization of Nonquaternary Reactivators of Acetylcholinesterase Inhibited by Organophosphorus Nerve Agents.
J Med Chem, 61 (17): 7630-7639. [PMID:30125110]