Towards small-molecule CXCR3 ligands with clinical potential
Maikel Wijtmans1, Dennis Verzijl, Rob Leurs
1Leiden/Amsterdam Center for Drug Research, Division of Medicinal Chemistry, Faculty of Sciences, VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands. wijtmans@few.vu.nl
Small molecule drugs targeting the CXCR3 receptor show promise for inflammatory diseases. While some CXCR3 antagonists proved effective in animal studies, clinical trials revealed limitations, necessitating further development of novel drug classes.
Area of Science:
- Immunology
- Pharmacology
Background:
- The chemokine receptor CXCR3 is implicated in numerous inflammatory diseases.
- Understanding CXCR3's role is crucial for developing targeted therapies.
Purpose of the Study:
- To review the development of small molecule CXCR3 ligands.
- To evaluate their therapeutic potential in inflammatory conditions.
Main Methods:
- Literature review of CXCR3 antagonist development.
- Analysis of preclinical and clinical trial data for CXCR3-targeting compounds.
Main Results:
- Multiple classes of CXCR3 antagonists with diverse structures have been identified.
- Some antagonists demonstrated efficacy in animal models of disease.
- The clinical candidate AMG487 was withdrawn in Phase II due to insufficient efficacy.
Conclusions:
- CXCR3 antagonism holds therapeutic promise for inflammatory diseases.
- Further research into novel antagonist classes is required to fully realize CXCR3's therapeutic potential.
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