Recent progress in the development of antagonists to the chemokine receptors CCR3 and CCR4

被引:64
作者
Pease, James Edward [1 ,2 ]
Horuk, Richard [3 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Fac Med, MRC, London SW7 2AZ, England
[2] Asthma UK Ctr Allerg Mech Asthma, Leukocyte Biol Sect, London SW7 2AZ, England
[3] Univ Calif Davis, Dept Pharmacol, Davis, CA 95616 USA
基金
英国医学研究理事会;
关键词
antagonists; asthma; autoimmune; CCR3; CCR4; chemokine; inflammation; ACTIVATION-REGULATED CHEMOKINE; MACROPHAGE-DERIVED CHEMOKINE; GENE-RELATED PEPTIDE; INDUCED AIRWAY INFLAMMATION; SMALL-MOLECULE ANTAGONISTS; CELLS IN-VITRO; EPITHELIAL-CELLS; INDAZOLE ARYLSULFONAMIDES; DIFFERENTIAL EXPRESSION; MACULAR DEGENERATION;
D O I
10.1517/17460441.2014.897324
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction: The chemokine receptors CCR3 and CCR4 have been shown to be important therapeutic targets for the treatment of a variety of diseases. Although only two chemokine receptor inhibitors have been approved so far, there are numerous compounds that are in various stages of development. Areas covered: In this review article, the authors provide an update on the progress made in the identification of antagonists against the chemokine receptors CCR3 and CCR4 from 2009 to the present. The rationale of writing this review article is to cover the most important approaches to identifying antagonists to these two receptors, which could prove to be useful therapeutics in treating proinflammatory diseases. Expert opinion: Pharmaceutical companies have expended a considerable amount of money and effort to identify potent inhibitors of CCR3 and CCR4 for the treatment of asthma and atopic diseases. Although a variety of compounds have been described and several have progressed into the clinic, none have so far made it as approved drugs. There are, however, novel approaches such as mogamulizumab, a monoclonal antibody to CCR4 currently is in clinical trials for cancer and ASM8, an antisense nucleotide to CCR3, which is in Phase II clinical trials for asthma that might still prove to be successful new therapeutics.
引用
收藏
页码:467 / 483
页数:17
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