Horuk Richard
Richard Horuk is an adjunct professor at Touro University, 1310 Johnson Lane, Vallejo, California 94592, USA.
Nat Rev Drug Discov. 2009 Jan;8(1):23-33. doi: 10.1038/nrd2734. Epub 2008 Dec 12.
Chemokine receptors have a key role in the pathogenesis of autoimmune diseases, inflammation and viral infection. However, with the exception of selective CCR5 antagonists for HIV, the promise of obtaining new therapeutics related to chemokine receptors has not yet been realized. This article highlights some of the recent failures in the clinical trials of chemokine receptor antagonists and explores possible reasons as to why this might have occurred. Such reasons include the lack of predictability of animal models and redundancy of the target. A potential solution could be to develop drugs that target more than one receptor--known as polypharmacology--which could be a novel way to generate effective therapeutics.
趋化因子受体在自身免疫性疾病、炎症和病毒感染的发病机制中起着关键作用。然而，除了用于治疗艾滋病的选择性CCR5拮抗剂外，与趋化因子受体相关的新型治疗方法的前景尚未实现。本文着重介绍了趋化因子受体拮抗剂临床试验中最近出现的一些失败案例，并探讨了出现这种情况的可能原因。这些原因包括动物模型缺乏可预测性以及靶点的冗余性。一个潜在的解决方案可能是开发针对多种受体的药物——即所谓的多药理学——这可能是产生有效治疗方法的一种新途径。
