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细胞凋亡:新药研发的潜在治疗靶点

Apoptosis: potential therapeutic targets for new drug discovery.

作者信息

Jana Snehasis, Paliwal Jyoti

机构信息

Metabolism and Pharmacokinetics Division, New Drug Discovery and Research, Ranbaxy Research Laboratories, Plot-20, Sector-18, Udyog Vihar, Industrial Area, Gurgaon, Haryana 122015, India.

出版信息

Curr Med Chem. 2007;14(22):2369-79. doi: 10.2174/092986707781745569.

Abstract

Apoptosis is involved in a wide range of pathologic conditions, including neurodegenerative, autoimmune diseases, cardiovascular diseases and cancer. Therefore, the ability to understand and manipulate the cell death machinery is an obvious goal of medical research. Novel therapeutic approaches to modulate disease by regulating apoptosis are being tested in preclinical and clinical settings. Approaches include the traditional use of small molecules to target specific players in the apoptosis cascade. As our understanding of apoptosis increases, further opportunities will arise for tailor-made therapies that will result in improved clinic. From variety of compounds are discovered in this field and only few are found in the preclinical and clinical trials. The lack of specific potent nonpeptide apoptosis inducers and/or inhibitors has limited for a long time the clinical investigation of this target. But in the last few years the renewed interest of pharmaceutical companies has been giving a strong impulse to the research in this area. This review considers the molecular mechanisms of apoptosis and their interaction in regulation of apoptosis. We also focus on recent developments of nonpeptide apoptosis modulators and their progress in drug lead discovery.

摘要

细胞凋亡涉及广泛的病理状况,包括神经退行性疾病、自身免疫性疾病、心血管疾病和癌症。因此,理解和操控细胞死亡机制的能力显然是医学研究的一个目标。通过调节细胞凋亡来调控疾病的新型治疗方法正在临床前和临床环境中进行测试。这些方法包括传统地使用小分子来靶向细胞凋亡级联反应中的特定参与者。随着我们对细胞凋亡的理解不断加深,将会出现更多量身定制的疗法,从而改善临床疗效。在这个领域发现了各种各样的化合物,但只有少数进入了临床前和临床试验。长期以来,缺乏特异性强效非肽类细胞凋亡诱导剂和/或抑制剂限制了对该靶点的临床研究。但在过去几年中,制药公司重新燃起的兴趣极大地推动了该领域的研究。本综述探讨了细胞凋亡的分子机制及其在细胞凋亡调控中的相互作用。我们还重点关注非肽类细胞凋亡调节剂的最新进展及其在药物先导物发现方面的进展。

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