Clinical significance of chemokine receptor antagonists.

: Chemokine receptors are important therapeutic targets for the treatment of many human diseases. This study will provide an overview of approved chemokine receptor antagonists and promising candidates in advanced clinical trials.: We will describe clinical aspects of chemokine receptor antagonists regarding their clinical efficacy, mechanisms of action, and re-purposed applications.: Three chemokine antagonists have been approved: (i) plerixafor is a small-molecule CXCR4 antagonist that mobilizes hematopoietic stem cells; (ii) maraviroc is a small-molecule CCR5 antagonist for anti-HIV treatment; and (iii) mogamulizumab is a monoclonal-antibody CCR4 antagonist for the treatment of mycosis fungoides or Sézary syndrome. Moreover, phase 3 trials are ongoing to evaluate many potent candidates, including CCR5 antagonists (e.g. leronlimab), dual CCR2/CCR5 antagonists (e.g. cenicriviroc), and CXCR4 antagonists (e.g. balixafortide, mavorixafor, motixafortide). The success of chemokine receptor antagonists depends on the selective blockage of disease-relevant chemokine receptors which are indispensable for disease progression. Although clinical translation has been slow, antagonists targeting chemokine receptors with multifaced functions offer the potential to treat a broad spectrum of human diseases.