首创的洛伐他汀和后继药物

发布时间：2018-03-09 21:04

本文选题：洛伐他汀　切入点：真菌细胞壁　出处：《药学学报》2015年01期 　论文类型：期刊论文

【摘要】：新药创制是复杂的智力活动,涉及科学研究、技术创造、产品开发和医疗效果等多维科技活动。每个药物都有自身的研发轨迹,而构建化学结构是最重要的环节,因为它涵盖了药效、药代、安全性和生物药剂学等性质。本栏目以药物化学视角,对有代表性的药物的成功构建,加以剖析和解读。体内胆固醇合成的基础研究阐明了级联生化反应的全过程,解析了参与反应的酶系和生成的各个中间体的生化机制,这为研发降胆固醇药物提供了靶标和评价活性的生物标志物。临床发现血浆中胆固醇水平与发生冠心病的相关性,成为研发降胆固醇药物的动因和依据。基础和临床研究的互动,催生了洛伐他汀等HMG-Co A还原酶抑制剂的研发,彰显了转化医学研发特征。在项目实施上,科学家根据真菌细胞壁中没有胆固醇而是麦角甾醇,作出了"真菌体内有抑制胆固醇生成的物质"的科学假设,通过实验求证,在青霉菌中发现了有价值的活性物质,揭示了继青霉素之后青霉菌对人类的又一重要"贡献"。然而研发洛伐他汀并不顺利,一波三折的历程折射出科学家的百折不挠、不轻易放弃和在细节处求真知的科学精神,成功地开辟了治疗心血管疾病的崭新药物领域。后继研发的他汀,在安全有效性乃至抑酶的热力学特征等多层面上优胜于洛伐他汀,后来者居上。然而首创药物功不可没。
[Abstract]:The creation of new drugs is a complex intellectual activity involving multi-dimensional scientific and technological activities such as scientific research, technological creation, product development and medical effects. Each drug has its own research and development track, and the construction of chemical structures is the most important link. Because it covers the properties of pharmacodynamics, pharmacology, safety and biopharmaceuticals. The basic research on cholesterol synthesis in vivo clarifies the whole process of cascade biochemical reaction, the biochemical mechanism of the enzymes involved in the reaction and the various intermediates produced, This provides a biomarker for the development of cholesterol-lowering drugs. Clinical findings show that plasma cholesterol levels are associated with coronary heart disease. The interaction between basic and clinical studies has spawned the development of HMG-Co A reductase inhibitors, such as lovastatin, and highlighted the R & D characteristics of transformational medicine. On the basis of the scientific hypothesis that there is no cholesterol in the cell wall of fungi but ergosterol, scientists have made the scientific hypothesis that there is a substance that inhibits cholesterol production in fungi. Through experiments, they have found valuable active substances in Penicillium. It reveals another important "contribution" of Penicillium to mankind after penicillin. However, the development of lovastatin has not been smooth, and the twists and turns of the process reflect the scientific spirit of scientists who are indomitable, unwilling to give up and to know in detail. It has successfully opened up a new field of medicine for the treatment of cardiovascular disease. The latter one is superior to lovastatin in many aspects, such as safety, effectiveness and thermodynamics of enzyme inhibition.
【作者单位】：中国医学科学院药物研究所;
【分类号】：R972

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