To discover new lead compounds for M1 agonists. Ten typical M1 agonists were superimposed to build a M1 agonists 3D-pharmacophore model using distance-comparisons （DISCO） method without the previous knowledge of the...To discover new lead compounds for M1 agonists. Ten typical M1 agonists were superimposed to build a M1 agonists 3D-pharmacophore model using distance-comparisons （DISCO） method without the previous knowledge of the three-dimensional structure of M1 receptor. Virtual screening strategy was used to analyze the Available Chemicals Directory-Screening Compounds （ACD-SC） to identify possible new hits. Twenty-two compounds which fit the pharmacophore model well and are not similar with known M1 agonists were purchased in order to evaluate their M1 receptor agonist activity. One of them shows M1 receptor agonist activity with EC50 of 4.90 μmol/L and maximum response. Multiple of 10.0 which shows it worthy of further study as a new lead compound for M1 agonists.展开更多
在分子设计研究中,DISCO 可用于搜寻结构相似的活性化合物可能存在的药效团模型,并定性预测相似结构化合物是否具有活性。本文在简要介绍 DISCO 方法后,将其应用于一组菊酯类和一组腙类化合物的药效团模型搜寻,以及相似结构化合物的定...在分子设计研究中,DISCO 可用于搜寻结构相似的活性化合物可能存在的药效团模型,并定性预测相似结构化合物是否具有活性。本文在简要介绍 DISCO 方法后,将其应用于一组菊酯类和一组腙类化合物的药效团模型搜寻,以及相似结构化合物的定性活性判断。展开更多
2018 Xue Wei Tomb#1(XWT1 for short)has recently been listed among the top ten new archeological discoveries from across China in 2020.This giant tomb is seated in a Tubo-period graveyard along the northern riverbanks ...2018 Xue Wei Tomb#1(XWT1 for short)has recently been listed among the top ten new archeological discoveries from across China in 2020.This giant tomb is seated in a Tubo-period graveyard along the northern riverbanks of Chahanwusu in Reshui Township of Dulan,Qinghai Province,and is a close neighbor to another giant graveyard named the Nine-Tier Ghostly Tower.展开更多
基金National Natural Science Foundation of China (Grant No. 30271538)985 program,Ministry of Education of China
文摘To discover new lead compounds for M1 agonists. Ten typical M1 agonists were superimposed to build a M1 agonists 3D-pharmacophore model using distance-comparisons （DISCO） method without the previous knowledge of the three-dimensional structure of M1 receptor. Virtual screening strategy was used to analyze the Available Chemicals Directory-Screening Compounds （ACD-SC） to identify possible new hits. Twenty-two compounds which fit the pharmacophore model well and are not similar with known M1 agonists were purchased in order to evaluate their M1 receptor agonist activity. One of them shows M1 receptor agonist activity with EC50 of 4.90 μmol/L and maximum response. Multiple of 10.0 which shows it worthy of further study as a new lead compound for M1 agonists.
文摘2018 Xue Wei Tomb#1(XWT1 for short)has recently been listed among the top ten new archeological discoveries from across China in 2020.This giant tomb is seated in a Tubo-period graveyard along the northern riverbanks of Chahanwusu in Reshui Township of Dulan,Qinghai Province,and is a close neighbor to another giant graveyard named the Nine-Tier Ghostly Tower.
