Protein crystallography and drug discovery: recollections of knowledge exchange between academia and industry.
Protein crystallography and drug discovery: recollections of knowledge exchange between academia and industry.
复制标题
蛋白质晶体学和药物发现：学术界与工业之间知识交流的回忆。
DOI：
10.1107/s2052252517009241
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发表时间：
2017-07-01
期刊：
影响因子：
3.9
通讯作者：
Blundell TL
中科院分区：
文献类型：
--
作者：
Blundell TL
结构导向的药物发现是蛋白质晶体学的应用和学术界与工业界之间知识交流的故事。它导致美国食品和药物管理局批准了新药，并有望在发展中国家治疗罕见遗传病和传染病。结构导向药物发现的发展是一个知识交流的故事，新的想法来自研究生态系统的各个部分。多萝西·克劳福特·霍奇金在20世纪30年代从Boots Pure Drug Company获得胰岛素，并在20世纪50年代在Novo公司优化了胰岛素结晶，使其结构在牛津大学得以确定。为了满足制药业开发抗高血压药物的需求，学术界（这次是在伦敦）开发了血浆蛋白酶的结构。二聚天冬氨酸蛋白酶的想法来自一个国际学术团队，并在HIV中被发现;它最终导致了新的HIV抗病毒药物在工业中的开发。基于结构引导的片段发现是在大型制药和生物技术中开发的，但在学术界已被用于开发靶向蛋白质-蛋白质相互作用的新抑制剂以及对抗结核病等分枝杆菌感染的抗菌剂。这些观察结果有力地反驳了所谓的“线性模型”，即思想只从学术机构流向工业界。结构导向药物发现是蛋白质晶体学的应用和学术界与工业界之间的知识交流的故事，导致美国食品和药物管理局批准用于癌症和其他常见医疗条件的新药，以及治疗罕见遗传疾病和传染病的希望，这些疾病在发展中国家特别具有挑战性。
Structure-guided drug discovery is a story of applications of protein crystallography and knowledge exchange between academia and industry. It has led to new drug approvals by the Food and Drug Administration in the USA and hope for treatment of rare genetic diseases and infectious diseases in the developing world. The development of structure-guided drug discovery is a story of knowledge exchange where new ideas originate from all parts of the research ecosystem. Dorothy Crowfoot Hodgkin obtained insulin from Boots Pure Drug Company in the 1930s and insulin crystallization was optimized in the company Novo in the 1950s, allowing the structure to be determined at Oxford University. The structure of renin was developed in academia, on this occasion in London, in response to a need to develop antihypertensives in pharma. The idea of a dimeric aspartic protease came from an international academic team and was discovered in HIV; it eventually led to new HIV antivirals being developed in industry. Structure-guided fragment-based discovery was developed in large pharma and biotechs, but has been exploited in academia for the development of new inhibitors targeting protein–protein interactions and also antimicrobials to combat mycobacterial infections such as tuberculosis. These observations provide a strong argument against the so-called ‘linear model’, where ideas flow only in one direction from academic institutions to industry. Structure-guided drug discovery is a story of applications of protein crystallography and knowledge exhange between academia and industry that has led to new drug approvals for cancer and other common medical conditions by the Food and Drug Administration in the USA, as well as hope for the treatment of rare genetic diseases and infectious diseases that are a particular challenge in the developing world.