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Substrate Activity Screening (SAS) and Related Approaches in Medicinal Chemistry
Author(s) -
Gladysz Rafaela,
Lambeir AnneMarie,
Joossens Jurgen,
Augustyns Koen,
Van der Veken Pieter
Publication year - 2016
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201500569
Subject(s) - drug discovery , substrate (aquarium) , substrate specificity , computational biology , identification (biology) , fragment (logic) , chemistry , combinatorial chemistry , biochemical engineering , computer science , enzyme , biochemistry , biology , engineering , ecology , botany , programming language
Substrate activity screening (SAS) was presented a decade ago by Ellman and co‐workers as a straightforward methodology for the identification of fragment‐sized building blocks for enzyme inhibitors. Ever since, SAS and variations derived from it have been successfully applied to the discovery of inhibitors of various families of enzymatically active drug targets. This review covers key achievements and challenges of SAS and related methodologies, including the modified substrate activity screening (MSAS) approach. Special attention is given to the kinetic and thermodynamic aspects of these methodologies, as a thorough understanding thereof is crucial for successfully transforming the identified fragment‐sized hits into potent inhibitors.