Molecular Approaches to Receptors as Targets for Drug Discovery

Abstract The cloning of a great number of receptors and channels has revealed that many of these targets for drug discovery can be grouped into superfamilies based on sequence and structural similarities. This review presents an overview of how molecular biological approaches have revealed a plethor...

Full description

Saved in:
Bibliographic Details
Published in:Journal of receptors and signal transduction 1997-01, Vol.17 (5), p.671-776
Main Authors: Herz, Jeffrey M., Thomsen, William J., Yarbrough, George G.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Drug Design
GTP-Binding Proteins - physiology
Humans
Ion Channel Gating - physiology
Ion Channels - physiology
Models, Molecular
Molecular Sequence Data
Receptors, Cell Surface - classification
Receptors, Cell Surface - drug effects
Receptors, Cell Surface - physiology
Terminology as Topic
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract The cloning of a great number of receptors and channels has revealed that many of these targets for drug discovery can be grouped into superfamilies based on sequence and structural similarities. This review presents an overview of how molecular biological approaches have revealed a plethora of receptor subtypes, led to new definitions of subtypes and isoforms, and played a role in the development of highly selective drugs. Moreover, the diversity of subtypes has molded current views of the structure and function of receptor families. Practical difficulties and limitations inherent in the characterization of the ligand binding and signaling properties of expressed recombinant receptors are discussed. The importance of evaluating drug-receptor interactions that differ with temporally transient and distinct receptor conformational states is emphasized. Structural motifs and signal transduction features are presented for the following major receptor superfamilies: ligand-gated ion channel, voltage-dependent ion channel, G-protein coupled, receptor tyrosine-kinase, receptor protein tyrosine-phosphatase, cytokine and nuclear hormone. In addition, a prototypic receptor is analyzed to illustrate functional properties of a given family. The review concludes with a discussion of future directions in receptor research that will impact drug discovery, with a specific focus on orphan receptors as targets for drug discovery. Methods for classifying orphan receptors based upon homologies with members of existing superfamilies are presented together with molecular approaches to the greater challenge of defining their physiological roles. Besides revealing new orphan receptors, the human genome sequencing project will result in the identification of an abundance of novel receptors that will be molecular targets for the development of highly selective drugs. These findings will spur the discovery and development of an exciting new generation of receptor-subtype specific drugs with enhanced therapeutic specificity.
ISSN:1079-9893
1532-4281
DOI:10.3109/10799899709044284