title: Substrate Activity Screening (SAS) and Related Approaches in Medicinal Chemistry.
abstract: 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.
authors: Medicinal Chemistry (UAMC), Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium.
authors: Rafaela
authors: R
authors: Gladysz
authors: Laboratory of Medical Biochemistry, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium.
authors: Anne-Marie
authors: AM
authors: Lambeir
authors: Medicinal Chemistry (UAMC), Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium.
authors: Jurgen
authors: J
authors: Joossens
authors: Medicinal Chemistry (UAMC), Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium.
authors: Koen
authors: K
authors: Augustyns
authors: Medicinal Chemistry (UAMC), Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium. pieter.vanderveken@uantwerpen.be.
authors: Pieter
authors: P
authors: Van der Veken
mesh_terms: D002626:Chemistry, Pharmaceutical; D004353:Drug Evaluation, Preclinical; D013379:Substrate Specificity; D013816:Thermodynamics
keywords: MSAS; SAS; fragment-based drug design; inhibitors; substrate activity screening