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Structure‐Based and Fragment‐Based GPCR Drug Discovery
Author(s) -
Andrews Stephen P.,
Brown Giles A.,
Christopher John A.
Publication year - 2014
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.201300382
Subject(s) - g protein coupled receptor , drug discovery , computational biology , identification (biology) , biology , drug , receptor , bioinformatics , pharmacology , genetics , botany
G protein‐coupled receptors (GPCRs) are an important family of membrane proteins; historically, drug discovery in this target class has been fruitful, with many of the world’s top‐selling drugs being GPCR modulators. Until recently, the modern techniques of structure‐ and fragment‐based drug discovery had not been fully applied to GPCRs, primarily because of the instability of these proteins when isolated from their cell membrane environments. Recent advances in receptor stabilisation have facilitated major advances in GPCR structural biology over the past six years, with 21 new receptor targets successfully crystallised with one or more ligands. The dramatic increase in GPCR structural information has yielded an increased use of structure‐based methods for hit identification and progression, which are reviewed herein. Additionally, a number of fragment‐based drug discovery techniques have been validated for use with GPCRs in recent years; these approaches and their use in hit identification are reviewed.