Chemokine receptors are G protein-coupled receptors (GPCRs) that respond to stimulation by small protein chemotactic cytokines (chemokines), and orchestrate the migration of immune cells toward sites of infection and inflammation. Twenty-two chemokine receptors are currently known in humans: eighteen conventional (cCKRs) and four atypical (ACKRs) receptors that function in multiple processes in normal physiology and in disease. Although chemokine receptors are validated therapeutic targets and many chemokine receptor antagonists have been tested in clinical trials, only three, Plerixafor (the CXCR4 antagonist and hematopoietic stem cell mobilizer); Maraviroc (the CCR5 antagonist and anti-HIV agent); and the monoclonal antibody mogamulizumab targeting CCR4 in relapsed or refractory mycosis fungoides and Sézary disease, are approved for clinical use. Challenges in the discovery and development of antagonists of chemokine receptors range from imprecise definition of the roles of chemokine receptors in disease to difficulties with the identification of high-affinity inhibitors with low toxicity and sufficient specificity for their targets.
In this Research Topic, we aim to focus on the aspects of biology and protein structure that make chemokine receptors challenging therapeutic targets, and on novel approaches to advance the discovery and development of chemokine receptor antagonists.
We welcome the submission of Reviews and Original Research articles focusing on, but not limited to, the following sub-topics:
• Roles of chemokine receptors in health and disease
• Structural and functional features of chemokine receptors amenable to therapeutic targeting
• Roadblocks impeding therapeutic targeting of chemokine receptors
• Current progress with therapeutic targeting of chemokine receptors
• Strategies expediting the discovery of chemokine receptor antagonists
• Novel antagonists of chemokine receptors
Chemokine receptors are G protein-coupled receptors (GPCRs) that respond to stimulation by small protein chemotactic cytokines (chemokines), and orchestrate the migration of immune cells toward sites of infection and inflammation. Twenty-two chemokine receptors are currently known in humans: eighteen conventional (cCKRs) and four atypical (ACKRs) receptors that function in multiple processes in normal physiology and in disease. Although chemokine receptors are validated therapeutic targets and many chemokine receptor antagonists have been tested in clinical trials, only three, Plerixafor (the CXCR4 antagonist and hematopoietic stem cell mobilizer); Maraviroc (the CCR5 antagonist and anti-HIV agent); and the monoclonal antibody mogamulizumab targeting CCR4 in relapsed or refractory mycosis fungoides and Sézary disease, are approved for clinical use. Challenges in the discovery and development of antagonists of chemokine receptors range from imprecise definition of the roles of chemokine receptors in disease to difficulties with the identification of high-affinity inhibitors with low toxicity and sufficient specificity for their targets.
In this Research Topic, we aim to focus on the aspects of biology and protein structure that make chemokine receptors challenging therapeutic targets, and on novel approaches to advance the discovery and development of chemokine receptor antagonists.
We welcome the submission of Reviews and Original Research articles focusing on, but not limited to, the following sub-topics:
• Roles of chemokine receptors in health and disease
• Structural and functional features of chemokine receptors amenable to therapeutic targeting
• Roadblocks impeding therapeutic targeting of chemokine receptors
• Current progress with therapeutic targeting of chemokine receptors
• Strategies expediting the discovery of chemokine receptor antagonists
• Novel antagonists of chemokine receptors