Pharmacology and Personalised Medicine, Maastricht University, Maastricht, The Netherlands.
Pharmacology and Personalised Medicine, Maastricht University, Maastricht, The Netherlands; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
Trends Pharmacol Sci. 2022 Feb;43(2):136-150. doi: 10.1016/j.tips.2021.11.004. Epub 2021 Dec 9.
For complex diseases, most drugs are highly ineffective, and the success rate of drug discovery is in constant decline. While low quality, reproducibility issues, and translational irrelevance of most basic and preclinical research have contributed to this, the current organ-centricity of medicine and the 'one disease-one target-one drug' dogma obstruct innovation in the most profound manner. Systems and network medicine and their therapeutic arm, network pharmacology, revolutionize how we define, diagnose, treat, and, ideally, cure diseases. Descriptive disease phenotypes are replaced by endotypes defined by causal, multitarget signaling modules that also explain respective comorbidities. Precise and effective therapeutic intervention is achieved by synergistic multicompound network pharmacology and drug repurposing, obviating the need for drug discovery and speeding up clinical translation.
对于复杂疾病,大多数药物的疗效都很低,药物发现的成功率一直在下降。虽然大多数基础研究和临床前研究的质量低、可重复性问题以及转化相关性差都对此有所贡献,但目前以器官为中心的医学模式和“一种疾病-一个靶点-一种药物”的教条以最深刻的方式阻碍了创新。系统和网络医学及其治疗手段——网络药理学——彻底改变了我们定义、诊断、治疗和理想情况下治愈疾病的方式。描述性疾病表型被由因果关系、多靶点信号模块定义的内表型所取代,这些模块也解释了各自的合并症。通过协同的多化合物网络药理学和药物再利用实现精确有效的治疗干预,避免了药物发现的需要并加快了临床转化。