Designing small molecule CXCR3 antagonists.
File(s)Desigining small molecule CXCR3 ACCEPTED.pdf (1.24 MB)
Accepted version
Author(s)
Pease, JE
Type
Journal Article
Abstract
INTRODUCTION: By virtue of its specificity for chemokines induced in Th1-associated pathologies, CXCR3 has attracted considerable attention as a target for therapeutic intervention. Several pharmacologically distinct small molecules with in vitro and in vivo potency have been described in the literature, although to date, none have shown efficacy in clinical trials. Areas covered: In this article, the author outlines the rationale for targeting CXCR3 and discusses the potential pitfalls in targeting receptors in poorly understood areas of chemokine biology. Furthermore, they cover emerging therapeutic areas outside of the 'traditional' Th1 arena in which CXCR3 antagonists may ultimately bear fruit. Finally, they discuss the design of recently discovered small molecules targeting CXCR3. Expert opinion: CXCR3 and its ligands appear to play roles in a multitude of diverse diseases in humans. In vitro studies suggest that CXCR3 is inherently 'druggable' and that potent, efficacious small molecules targeting CXCR3 antagonists will find a clinical niche. However, the well-trodden path to failure of small molecule chemokine receptor antagonists in clinical trials suggests that a cautious approach should be undertaken. Ideally, unequivocal evidence elucidating the precise role of CXCR3 should be obtained before targeting the receptor in a particular disease cohort.
Date Issued
2016-12-30
Online Publication Date
2017-12-30T07:00:19Z
Date Acceptance
2016-12-01
ISSN
1746-045X
Publisher
Taylor & Francis
Start Page
159
End Page
168
Journal / Book Title
Expert Opinion on Drug Discovery
Volume
12
Issue
2
Copyright Statement
© 2016 Taylor & Francis. This is an Accepted Manuscript of an article published by Taylor & Francis in Expert Opinion on Drug Discovery on 30 Dec 2016, available online: http://www.tandfonline.com/10.1080/17460441.2017.1268597
Source Database
pubmed
Sponsor
Arthritis Research UK
Identifier
http://www.ncbi.nlm.nih.gov/pubmed/28010133
Grant Number
18303
Subjects
CXCR3
Chemokine receptor
chemokine receptor antagonist
inflammation
Pharmacology & Pharmacy
Publication Status
Published
Country
England