Clinical Chemokine Targets
Relevant Clinical Targets
Chemokines are clinical targets because they play a pivotal role in immune responses, inflammation, and cell migration, making them key players in various diseases, including cancer, autoimmune disorders, and chronic inflammatory conditions. By targeting chemokines or their receptors, researchers and clinicians aim to modulate immune cell trafficking, suppress inflammation, enhance anti-tumor immune responses, and improve the efficacy of treatments. These efforts hold promise for developing innovative therapies and personalized medicine approaches to manage and combat a wide range of diseases.
Examples of medications targeting chemokines or chemokine receptors:
- Maraviroc (Selzentry/Celsentri): Maraviroc is an FDA-approved medication for the treatment of HIV/AIDS. It is a CCR5 antagonist that blocks the CCR5 chemokine receptor, preventing the entry of the HIV virus into host cells. This medication is an example of targeting chemokine receptors to inhibit viral infection.
- Tofacitinib (Xeljanz): Tofacitinib is used to treat autoimmune conditions such as rheumatoid arthritis, psoriasis, and ulcerative colitis. It inhibits Janus kinase (JAK) enzymes, which play a role in chemokine signaling and immune responses.
- Plerixafor (Mozobil): Plerixafor is used in combination with granulocyte colony-stimulating factor (G-CSF) to mobilize hematopoietic stem cells (HSCs) from the bone marrow into the bloodstream for collection in patients undergoing stem cell transplantation. It works by inhibiting the CXCR4 chemokine receptor.
- Mogamulizumab (Poteligeo): Mogamulizumab is an FDA-approved monoclonal antibody used to treat certain types of cutaneous T-cell lymphoma (CTCL). It targets the CCR4 chemokine receptor found on malignant T-cells.
- Vedolizumab (Entyvio): Vedolizumab is used to treat inflammatory bowel diseases like Crohn's disease and ulcerative colitis. It specifically targets the α4β7 integrin, which plays a role in immune cell trafficking to the gut through interaction with mucosal addressin cell adhesion molecule-1 (MAdCAM-1), a chemokine receptor.
- CCR2 Antagonists: Various CCR2 antagonists were in development for conditions like atherosclerosis, diabetic nephropathy, and inflammation-related disorders. Some examples include CCX140-B (C-C chemokine receptor 2 antagonist) and PF-04634817, although their clinical status may have changed.
- CXCR4 Inhibitors: Multiple compounds targeting the CXCR4 chemokine receptor were under investigation for cancer treatment and stem cell mobilization.