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文章旨在综述临床前药物研发的思路和过程,并结合笔者实验室的工作探讨如何高效开展药物研发,从而使新药从实验室到病床的转化能更成功顺利完成,且缩短时间。笔者主要针对再生医学(regenerative medicine)和癌症两个治疗领域,重点研究了7次跨膜蛋白细胞受体Smoothened和Frizzled的信号传导和信号通路调节,并以其作为新药靶分子,通过独创的高通量药物筛选平台,获得了许多高效、专一的小分子化合物。由于目前世界上尚无这类急需新药,我们对已经上市的“成熟药物”进行再定向,获得了能用于再生医学的特定糖皮质激素(针对Smoothened)和用于癌症治疗的氯硝柳胺(针对Frizzled)。通过多年努力,系统地建立了一个具有短、中、长期目标的创新药物研发体系。
The purpose of this article is to summarize the ideas and process of preclinical drug development, and to explore how to carry out drug research and development effectively in combination with the author’s laboratory work so that the transformation of new drugs from the laboratory to the hospital bed can be completed successfully and successfully, and the time can be shortened. The author focuses on two regenerative medicine and cancer therapeutic areas, focusing on seven transmembrane protein receptor Smoothened and Frizzled signal transduction and signaling pathway regulation, and as a new drug target molecules, through the original high Flux drug screening platform, access to many efficient, specific small molecule compounds. As there is no such urgently needed new drug in the world, we have redirected the already available “mature drugs” and obtained the specific glucocorticoids (for Smoothened) that can be used in regenerative medicine and the chlorinitrin for cancer treatment Diphenhydramine (for Frizzled). Through years of efforts, we have systematically established an innovative drug research and development system with short, medium and long-term goals.