化学
药物发现
血管紧张素II
受体
天然产物
高通量筛选
IC50型
组合化学
G蛋白偶联受体
抗高血压药
药理学
血管紧张素受体
生物化学
计算生物学
血压
体外
内科学
医学
生物
作者
Qi Liang,Jianyu He,Xue Zhao,Yan Xue,Haiyue Zuo,Xu Ru,Jun Yan,Jing Wang,Qian Li,Xinfeng Zhao
标识
DOI:10.1021/acs.jmedchem.1c00123
摘要
Natural products have failed to meet the urgent need for drug discovery in recent decades due to limited resources, necessitating new strategies for re-establishing the key role of natural products in hit screening. This work introduced DNA-encoding techniques into the synthesis of phenolic acid-focused libraries containing 32 000 diverse compounds. Online selection of the library using immobilized angiotensin II type I receptor (AT1R) resulted in seven phenolic acid derivatives. The half-maximal concentration (IC50) of hit 1 for the right shift of the [125I]-Sar1-AngII competition curve was 19.6 nM. Pharmacological examination of renovascular hypertensive rats demonstrated that hit 1 significantly lowered the blood pressure of the animals without changing their heart rates. These results were used to create a general strategy for rapid and unbiased discovery of hits derived from natural products with high throughput and efficiency.
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