ChemoCentryx, Inc., 850 Maude Avenue, Mountain View, California 94043, USA.
Nat Rev Immunol. 2011 May;11(5):355-63. doi: 10.1038/nri2972. Epub 2011 Apr 15.
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.
趋化因子及其受体是炎症过程的核心,是有吸引力的治疗靶点。抑制趋化因子受体的药物已被批准用于治疗 HIV 感染和干细胞动员,但尚未批准用于治疗炎症和/或自身免疫性疾病。我们分析了开发趋化因子受体拮抗剂所面临的挑战,并提出不合适的靶点选择和无效的给药剂量,而不是趋化因子系统的“冗余性”,是它们作为抗炎治疗的主要障碍。我们强调了一些证据,表明趋化因子受体抑制将被证明是炎症性疾病的有效治疗方法。