National Key Laboratory of Crop Genetic Improvement, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, P. R. China.
Trends Pharmacol Sci. 2010 Oct;31(10):443-8. doi: 10.1016/j.tips.2010.07.003. Epub 2010 Aug 18.
Conceptual innovations are needed to address the challenge of 'more investments, fewer drugs' in the pharmaceutical industry. Since the publication of The Origin of Species by Charles Darwin 150 years ago, evolution has been a central concept in biology. In this article, we show that evolutionary concepts are also helpful to streamline the drug-discovery pipeline through facilitating the discovery of targets and drug candidates. Furthermore, the antioxidant paradox can be addressed by an evolutionary methodology. Through examining the evolved biological roles of natural polyphenols (which dominate current antioxidant drug discovery), we reveal that polyphenols (particularly flavonoids) are not evolved for scavenging free radicals. This finding provides new clues to understanding why the strong in vitro antioxidant activities of polyphenols cannot be translated into in vivo effects. Polyphenols have evolved a superior ability to bind various proteins, so we also argue that they are good starting points for multi-target drugs.
需要进行概念创新，以应对制药行业“投入更多，产出更少”的挑战。自 150 年前查尔斯·达尔文（Charles Darwin）出版《物种起源》（The Origin of Species）以来，进化一直是生物学的核心概念。在本文中，我们表明，进化概念还有助于通过促进目标和药物候选物的发现来简化药物发现管道。此外，抗氧化悖论可以通过进化方法来解决。通过研究天然多酚（主导当前抗氧化药物发现）的进化生物作用，我们揭示了多酚（特别是类黄酮）不是为清除自由基而进化的。这一发现为理解为什么多酚的强体外抗氧化活性不能转化为体内作用提供了新的线索。多酚具有结合各种蛋白质的卓越能力，因此我们还认为它们是多靶标药物的良好起点。
