Serine Hydrolase Library
Designed for discovery of mild electrophilic inhibitors of the largest enzyme class
11 328 compounds
Serine hydrolases are important class of enzymes which include lipases, esterases, thioesterases, amidases, peptidases and proteases. They belong to one of the largest and most diverse classes of enzymes found in nature and represent ~1% of all proteins in mammalians playing vital roles in such pathophysiological processes as blood clotting, digestion, nervous system signalling, inflammation and cancer.
Despite the fact that pharmaceutical industry avoid developing therapeutics that form covalent bonds with protein targets, several commercialized serine hydrolase inhibitors as well as promising drug-candidates contain electrophilic chemical groups that interact covalently with Serine residue in the active site of their targets.
The library of mild electrophilic compounds has been plated for most convenient and quick access. Using our Serine hydrolase focused library you receive multiple benefits, allowing you to save on time and costs in hit expansion and optimization:
- Hit confirmation support – resupply of dry samples after QC check, samples repurification or resynthesis upon request.
- Analogs from dry stock of over 2.7 M compounds or REAL Space of 15.5 billion make-on-demand molecules.
- Straightforward & low-cost synthesis of follow-up libraries through our REAL Database technology
You have also an option to screen the librray directly at Enamine. In this case we will be happy to offer discount on library cost depending on the collaboration scope.
The main criterion of the selection was presence of the electrophilic groups (cyano, epoxide, carbonyl etc.), which can provide the key interaction with serine in the active site of targeted enzyme. Next we estimated the 3D-shape of the molecules and compared them by throughput docking with the volume of the active sites taken from X-ray data of several serine hydrolases. The compounds which did not fit to the active site were withdrawn.
Representative examples of commercialized serine hydrolase covalent inhibitors and examples of functional groups which usually bind in the active site.
In addition, we applied several MedChem structural filters in order to remove unattractive moieties, trivial chemotypes and enhance the library with compounds with the latest scaffolds, sp3-rich frameworks and peptidomimetic structural motifs.