Venkatesh S, Lipper R A
Biopharmaceutics R&D, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492, USA.
J Pharm Sci. 2000 Feb;89(2):145-54. doi: 10.1002/(SICI)1520-6017(200002)89:2<145::AID-JPS2>3.0.CO;2-6.
The R&D process for bringing drugs from discovery laboratories to the marketplace is undergoing rapid change, as enabled by new technologies and as demanded by the global pharmaceutical business environment. One consequence of the accelerated R&D paradigm is a blurring of the traditional discovery-development interface, which in turn impacts the traditional roles of discovery and development scientists. R&D organizations must find ways to screen out rapidly compounds that have relatively poor probability of successful registration. Quality of development candidates can be favorably influenced by early consideration of "developability" criteria along with receptor-based potency and specificity. Computational approaches and/or high-throughput experimental determinations will be used increasingly to profile compound characteristics which influence "developability." If such criteria are considered at the time of lead selection and optimization, the compound attrition rate during later development should be decreased from the historical norm. This article discusses the emerging role of development scientists during small-molecule lead selection and optimization. The changing role of development scientists also has implications for graduate curricula in the pharmaceutical sciences.
将药物从发现实验室推向市场的研发过程正在经历快速变革，这是由新技术推动以及全球制药商业环境的需求所导致的。加速研发模式的一个后果是传统的发现 - 开发界面变得模糊，这反过来又影响了发现和开发科学家的传统角色。研发组织必须找到方法，迅速筛选出成功注册可能性相对较低的化合物。通过早期考虑“可开发性”标准以及基于受体的效力和特异性，可以对开发候选物的质量产生有利影响。计算方法和/或高通量实验测定将越来越多地用于描绘影响“可开发性”的化合物特性。如果在先导化合物选择和优化时考虑这些标准，后期开发过程中的化合物淘汰率应低于历史常态。本文讨论了开发科学家在小分子先导化合物选择和优化过程中新兴的作用。开发科学家角色的变化也对制药科学的研究生课程产生了影响。
