1.Research advances in small-molecule hydrophobic tagging protein degraders
Zirui HUO ; Jieyu PEI ; Fangyi ZHAN ; Shaowen XIE ; Jinyi XU ; Shengtao XU
Journal of China Pharmaceutical University 2025;56(2):252-263
In In recent years, small-molecule targeted protein degraders inducing protein degradation have been developing rapidly. These molecules are attracting substantial interest from researchers since they can overcome such limitations of traditional small-molecule inhibitors as their inapplicability to ‘undruggable’ targets and tendency to induce drug resistance. Compared with other targeted protein degraders, small-molecule hydrophobic tags (HyTs) may have a smaller number of hydrogen bond donors/acceptors, smaller molecular weights, and better pharmacokinetic profiles, thus attracting extensive attention from researchers. This review focuses on the possible mechanisms and popular types of HyTs, with special attention to the potential application value of adamantane, a typical hydrophobic tag, in the fields of cancer and neurodegeneration. In general, there are still some problems like fewer types of hydrophobic tags and insufficient research on degradation mechanisms, which still need to be further explored. This review is expected to provide researchers working in the fields of small-molecule targeted protein degraders with some valuable reference.
2.Study on the Optimization of Purification Technology of Total Flavonoids from Amomum tsao-ko by Macroporous Adsorption Resin
Yuhong ZHAO ; Hua SHEN ; Shuangyi DAI ; Zhonghui PU ; Zirui XIE ; Ling XIAO ; Min KUANG ; Min DAI
China Pharmacy 2020;31(7):831-836
OBJECTIVE:To establish a method for the content determination of to tal flavonoids from Amomum tsao-ko ,and to optimize the purification technology by macroporous resin. METHODS :The content of total flavonoids was measured by HPLC. The determination was performed on Eclipse Plus C 18 column with mobile phase consisted of acetonitrile- 1% acetic acid solution (15∶85,V/V)at the flow rate of 0.8 mL/min. The column temperature was 40 ℃,and the detection wavelength was set at 256 nm. The sample size was 10 μL. Taking the adsorption and desorption performance as indexes,6 kinds of macroporous resins were screened out by static adsorption and desorption tests ;adsorption and desorption time were investigated by static adsorption and desorption kinetics tests. Using the content of total flavonoids (calculated by rutin )as index ,with sample concentration ,sample pH,ethanol volume fraction and elution amount as factors ,based on single factor test ,orthogonal design was used to optimize the purification technology of total flavonoids from A. tsao-ko ,and validation test was performed. RESULTS :The linear range of rutin were 0.028-0.281 mg/mL(r=0.999 9). The limit of quantification was 437.5 ng/mL and the limit of detection was 109.4 ng/mL. RSDs of precision ,stability and reproducibility tests were all lower than 2%;the recoveries were 96.24%-99.75%(RSD<2%,n= 6). The comprehensive capacity of adsorption and desorption of HPD 450 macroporous resin was the most suitable ,and the best static adsorption and desorption time both were 12 h. The optimal purification technology was 1.854 4 mg/mL ; ethanol elution was 8 times of the column volume. Vertificationtests show that after optimized ,the content of total flavonoids from A. tsao-ko increased from 22.556 7 mg/g to 57.728 2 mg/g. The purity of was 2.56 and stable for the content determination. Optimal purification technology is stable and feasible ,which is suitable for purifieation of total flavonoids from A. tsao-ko .