title: Overcoming hurdles in developing successful drugs targeting chemokine receptors.
abstract: Chemokines and their receptors are central to the inflammatory process and are attractive therapeutic targets. Drugs that inhibit chemokine receptors are approved for the treatment of HIV infection and for stem cell mobilization, but none have been approved yet for the treatment of inflammatory and/or autoimmune diseases. We analyse the challenges of developing chemokine receptor antagonists, and propose that inappropriate target selection and ineffective dosing, not the 'redundancy' of the chemokine system, are the main barriers to their use as anti-inflammatory therapies. We highlight evidence suggesting that chemokine receptor inhibition will prove to be an effective therapy in inflammatory diseases.
authors.affiliation: ChemoCentryx, Inc., 850 Maude Avenue, Mountain View, California 94043, USA. tschall@chemocentryx.com
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Schall
authors.forename: Amanda E I
authors.initials: AE
authors.lastname: Proudfoot
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology; D018925:Chemokines / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D055808:Drug Discovery; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D058990:Molecular Targeted Therapy; D054389:Receptors, CCR1 / Q000037:antagonists & inhibitors; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism
chemical_list: C515300:CCR1 protein, human; D018925:Chemokines; D054389:Receptors, CCR1; D019707:Receptors, Chemokine