Chemokines pp 87-117 | Cite as

Allosteric Modulation of Chemokine Receptors

  • Nuska Tschammer
  • Arthur Christopoulos
  • Terry Kenakin
Part of the Topics in Medicinal Chemistry book series (TMC, volume 14)


A central role of chemokines and their receptors in inflammatory processes has spurred numerous screening campaigns dedicated to the search for chemokine-receptor antagonists, which largely failed to deliver drugs for the treatment of inflammatory diseases. The quest for effective chemokine-receptor drug candidates thus continues, and the concept of allosteric targeting of the receptors may be the way forward. In this review, the complex allosteric mechanisms by which the functions of chemokines and their receptors are fine-tuned will be discussed and their impact on preclinical drug discovery presented. The opportunities and challenges of bench-to-clinic approaches are elucidated. We propose that while allosteric modulation of chemokine receptors adds a level of complexity to analyses and approaches to drug discovery, it also introduces a tremendous capacity for pharmacologic control of this physiological system for therapeutic advantage.


Chemokine Receptor CXCR4 Receptor Allosteric Site Probe Dependence Allosteric Effect 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Nuska Tschammer
    • 1
  • Arthur Christopoulos
    • 2
  • Terry Kenakin
    • 3
  1. 1.Department of Chemistry and Pharmacy, Medicinal Chemistry, Emil Fischer CenterFriedrich Alexander UniversityErlangenGermany
  2. 2.Department of Pharmacology, Drug Discovery Biology, Monash Institute of Pharmaceutical SciencesMonash UniversityParkvilleAustralia
  3. 3.Department of PharmacologyUniversity of North Carolina School of MedicineChapel HillUSA

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