Khan Abid, Greenman John, Archibald Stephen J
Department of Chemistry, The University of Hull, Cottingham Road, Hull, HU6 7RX, UK.
Curr Med Chem. 2007;14(21):2257-77. doi: 10.2174/092986707781696618.
Chemokine receptors are a target of growing interest for new therapeutic drugs, as their role in multiple disease states has been demonstrated. The CXCR4/ CXCL12 pairing has been implicated in HIV and cancer, as well as chronic inflammatory diseases, including asthma and rheumatoid arthritis. HIV uses CXCR4 or CCR5 receptors in the key binding step of the infection process, leading to the idea that drugs could be developed to block this interaction. Cancer metastasis has also been linked to cellular communication via the chemokine pathways and hence, receptor antagonists could potentially inhibit this important pathway of disease progression. A wealth of data concerning small molecule CXCR4 receptor antagonists has been generated over the last few years, as a variety of these small molecules have been tested, and the understanding of structure activity relationships has improved. Here, we review the developing area of small molecule CXCR4 antagonists and the rapidly increasing amount of data from biological studies. Both peptidic and non-peptidic compounds have been investigated. In particular, we focus on AMD3100 and bismacrocyclic analogues, the most extensively studied class of CXCR4 antagonists, and the recent developments in this area.
趋化因子受体作为新型治疗药物的靶点，其受关注程度日益增加，因为它们在多种疾病状态中的作用已得到证实。CXCR4/CXCL12配对与HIV、癌症以及包括哮喘和类风湿性关节炎在内的慢性炎症性疾病有关。HIV在感染过程的关键结合步骤中使用CXCR4或CCR5受体，这使得人们认为可以开发药物来阻断这种相互作用。癌症转移也与通过趋化因子途径进行的细胞通讯有关，因此，受体拮抗剂可能会抑制这一重要的疾病进展途径。在过去几年中，已经产生了大量关于小分子CXCR4受体拮抗剂的数据，因为已经测试了多种此类小分子，并且对构效关系的理解也有所提高。在此，我们综述小分子CXCR4拮抗剂这一不断发展的领域以及来自生物学研究的迅速增加的数据量。肽类和非肽类化合物均已得到研究。我们特别关注AMD3100和双大环类似物，这是研究最广泛的一类CXCR4拮抗剂，以及该领域的最新进展。
