Nucleotide pools in mammalian cells change due to the influence of antitumor drugs,which may help in evaluating the drug effect and understanding the mechanism of drug action.In this study,an ion-pair RP-HPLC method w...Nucleotide pools in mammalian cells change due to the influence of antitumor drugs,which may help in evaluating the drug effect and understanding the mechanism of drug action.In this study,an ion-pair RP-HPLC method was used for a simple,sensitive and simultaneous determination of the levels of 12 nucleotides in mammalian cells treated with antibiotic antitumor drugs(daunorubicin,epirubicin and dactinomycin D).Through the use of this targeted metabolomics approach to find potential biomarkers,UTP and ATP were verified to be the most appropriate biomarkers.Moreover,a holistic statistical approach was put forward to develop a model which could distinguish 4 categories of drugs with different mechanisms of action.This model can be further validated by evaluating drugs with different mechanismsof action.This targeted metabolomics study may provide a novel approach to predict the mechanism of action of antitumor drugs.展开更多
The first “deuterated” drug has recently been approved by the U.S. FDA (Food & Drug Administration). A “deuterated” drug is a drug in which the hydrogen atom in one or more of the carbon-hydrogen bonds in its ...The first “deuterated” drug has recently been approved by the U.S. FDA (Food & Drug Administration). A “deuterated” drug is a drug in which the hydrogen atom in one or more of the carbon-hydrogen bonds in its chemical structure is replaced by deuterium (“heavy hydrogen”, a hydrogen isotope that has a neutron, i.e., one neutron instead of the usual no neutrons). A carbon-deuterium (C-D) bond is more stable in the body than a carbon-hydrogen (C-H) bond. If the deuterium is strategically located in a drug’s chemical structure, the extra stability of the bond will be more resistant to metabolic breakdown, and the duration of drug action will be prolonged. We review the general concept of deuterated drugs, historical examples of the classes of application, and the new approval.展开更多
中药在逆转肺癌耐药中具有重要作用,而从中药中提取的单体化合物往往对于逆转肺癌耐药也有较好的活性。为了解目前不同结构中药单体化合物在肺癌多药耐药中的研究进展,本文以中药单体、肺癌、耐药性等为关键词在PubMed、Web of Science...中药在逆转肺癌耐药中具有重要作用,而从中药中提取的单体化合物往往对于逆转肺癌耐药也有较好的活性。为了解目前不同结构中药单体化合物在肺癌多药耐药中的研究进展,本文以中药单体、肺癌、耐药性等为关键词在PubMed、Web of Science、中国知网、维普、万方等数据库对中药单体成分逆转肺癌耐药的相关研究文献进行了检索,归纳了有关的中药单体类化合物,如生物碱类、萜类、黄酮类、皂苷类等化合物,综述了其在逆转肺癌耐药的作用及机制,从而可以为其进一步研究提供参考和思路。展开更多
目的:研究治疗便血方剂的用药规律及其“核心配伍-作用靶点”的关联性。方法:从《中医方剂大辞典》中筛选治疗便血的方剂,录入数据库,进行频数、聚类和关联分析,从中发现配伍组方规律。找到核心配伍组合后,再使用中药分子机制的生物信...目的:研究治疗便血方剂的用药规律及其“核心配伍-作用靶点”的关联性。方法:从《中医方剂大辞典》中筛选治疗便血的方剂,录入数据库,进行频数、聚类和关联分析,从中发现配伍组方规律。找到核心配伍组合后,再使用中药分子机制的生物信息学分析工具(Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine,BATMAN-TCM)对核心配伍组合进行活性成分-靶点预测,从而分析核心配伍组合的共同作用靶点。结果:共收录便血方剂616首,涉及中药340味;排名前10的高频药物依次是当归、甘草、黄连、芍药、枳壳、生地黄、黄芩、地榆、槐花、黄芪;主要使用的中药类别依次是补虚药、清热药、止血药。发现生地黄、黄芩、赤芍,人参、白术、茯苓,侧柏叶、地榆、槐花,当归和川芎等是治疗便血的四组核心配伍组合;经分析发现这四组核心配伍组合均有AR、ESR1、NR3C1、PGR、VDR这5个共同作用靶点,即治疗便血的11个核心药物有5个共同作用靶点。结论:《中医方剂大辞典》所载便血方剂的核心配伍组合关联的AR、NR3C1、PGR、VDR等靶点与肠炎、结直肠癌、胃癌等常导致便血的相关疾病密切相关,提示其“核心配伍-作用靶点”的关联性对于指导临床用药以及相关基础研究和新药开发有一定参考意义。展开更多
基金supported financially by the Natural Science Foundation of Liaoning Province,China (No.201102210)the Program for Liaoning Innovative Research Team in University (No.LH2012018)
文摘Nucleotide pools in mammalian cells change due to the influence of antitumor drugs,which may help in evaluating the drug effect and understanding the mechanism of drug action.In this study,an ion-pair RP-HPLC method was used for a simple,sensitive and simultaneous determination of the levels of 12 nucleotides in mammalian cells treated with antibiotic antitumor drugs(daunorubicin,epirubicin and dactinomycin D).Through the use of this targeted metabolomics approach to find potential biomarkers,UTP and ATP were verified to be the most appropriate biomarkers.Moreover,a holistic statistical approach was put forward to develop a model which could distinguish 4 categories of drugs with different mechanisms of action.This model can be further validated by evaluating drugs with different mechanismsof action.This targeted metabolomics study may provide a novel approach to predict the mechanism of action of antitumor drugs.
文摘The first “deuterated” drug has recently been approved by the U.S. FDA (Food & Drug Administration). A “deuterated” drug is a drug in which the hydrogen atom in one or more of the carbon-hydrogen bonds in its chemical structure is replaced by deuterium (“heavy hydrogen”, a hydrogen isotope that has a neutron, i.e., one neutron instead of the usual no neutrons). A carbon-deuterium (C-D) bond is more stable in the body than a carbon-hydrogen (C-H) bond. If the deuterium is strategically located in a drug’s chemical structure, the extra stability of the bond will be more resistant to metabolic breakdown, and the duration of drug action will be prolonged. We review the general concept of deuterated drugs, historical examples of the classes of application, and the new approval.
文摘中药在逆转肺癌耐药中具有重要作用,而从中药中提取的单体化合物往往对于逆转肺癌耐药也有较好的活性。为了解目前不同结构中药单体化合物在肺癌多药耐药中的研究进展,本文以中药单体、肺癌、耐药性等为关键词在PubMed、Web of Science、中国知网、维普、万方等数据库对中药单体成分逆转肺癌耐药的相关研究文献进行了检索,归纳了有关的中药单体类化合物,如生物碱类、萜类、黄酮类、皂苷类等化合物,综述了其在逆转肺癌耐药的作用及机制,从而可以为其进一步研究提供参考和思路。
文摘目的:研究治疗便血方剂的用药规律及其“核心配伍-作用靶点”的关联性。方法:从《中医方剂大辞典》中筛选治疗便血的方剂,录入数据库,进行频数、聚类和关联分析,从中发现配伍组方规律。找到核心配伍组合后,再使用中药分子机制的生物信息学分析工具(Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine,BATMAN-TCM)对核心配伍组合进行活性成分-靶点预测,从而分析核心配伍组合的共同作用靶点。结果:共收录便血方剂616首,涉及中药340味;排名前10的高频药物依次是当归、甘草、黄连、芍药、枳壳、生地黄、黄芩、地榆、槐花、黄芪;主要使用的中药类别依次是补虚药、清热药、止血药。发现生地黄、黄芩、赤芍,人参、白术、茯苓,侧柏叶、地榆、槐花,当归和川芎等是治疗便血的四组核心配伍组合;经分析发现这四组核心配伍组合均有AR、ESR1、NR3C1、PGR、VDR这5个共同作用靶点,即治疗便血的11个核心药物有5个共同作用靶点。结论:《中医方剂大辞典》所载便血方剂的核心配伍组合关联的AR、NR3C1、PGR、VDR等靶点与肠炎、结直肠癌、胃癌等常导致便血的相关疾病密切相关,提示其“核心配伍-作用靶点”的关联性对于指导临床用药以及相关基础研究和新药开发有一定参考意义。
