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《Drug discovery today》2022,27(6):1733-1742
Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action. 相似文献
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Mayuko Kinoshita Haruka Kaneko Lizu Liu Masashi Nagao Ryo Sadatsuki 《Modern rheumatology / the Japan Rheumatism Association》2019,29(1):157-164
Objectives: To examine the factors associated with increase in lumbar spine bone mineral density (LS-BMD) by bisphosphonates (BPs) with active vitamin D analog (aVD).Methods: Two independent postmenopausal osteoporotic patients treated by BPs with aVD for 24 months (Study 1: n?=?93, Study 2: n?=?99) were retrospectively analyzed.Results: In Study 1, LS-BMD of the patients significantly increased for 24 m (5.4%, p?.001). A multiple regression analysis among baseline characteristics revealed that serum calcium (sCa: 8.5–10.5?mg/dL) was associated with an increased LS-BMD by treatment (r2: 0.088, p?=?.02). While average sCa of the patients was 9.2?mg/dL before treatment, it increased time-dependently to 9.6?mg/dL for 24 m by treatment. As each patient had their LS-BMD five times during the study, there were four instances of %LS-BMD in each patient, resulting in 372 instances of %LS-BMD in Study 1. The smallest Akaike’s information criterion value for the most appropriate cut-off levels of sCa for %LS-BMD by treatment every 6 m was 9.3?mg/dL. The %LS-BMD by treatment for 6 m during 24 m period in patients with sCa ≥9.3?mg/dL (1.5%) was significantly higher than that in patients with sCa <9.3?mg/dL (0.8%, p?=?.038). The results of Study 2 were similar to those of Study 1, confirming the phenomena observed.Conclusion: sCa was associated with an increased LS-BMD by BPs with aVD. 相似文献
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中药(单体/复方)药效物质基础研究是中医药现代研究的关键问题之一。然而,目前运用的生化和分子生物学方法很难诠释其多靶点、整体性和动态性的整合调节作用。课题组提出的"证治代谢组学"假说理论指出,不同的证候存在"证相关代谢谱群"和"证相关生物标志物",这可能是中药药效物质基础所在,辨证论治后偏离的代谢网络功能呈现回归趋势。基于"证治代谢组学"假说开展中药(单体/复方)药效物质基础研究,这将为阐释中药(单体/复方)防病治病和养生保健的科学内涵及其对疾病个体的整合调节作用提供新的思路。本文以冠心病为研究载体、气阴虚血瘀证为切入点、活血保心丸为干预措施,就该研究思路的内涵与总体模式、提出的背景与依据、实践的方式与可行性、创新与特色及其研究意义等进行了简要介绍。 相似文献
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WT1基因位于人类染色体11p13,在80%的急性髓系白血病(acute myeloid leukemia,AML)患者中高表达,是AML预后不良的分子标志,可作为AML预后评估和微小残留病变(minimal residual disease,MRD)监测的有效指标。由于WT1在AML中均有异常高表达,故认为是一种AML抗原,可作为特异性免疫治疗的新靶点。一些小规模的临床试验证实以WT1为靶点的免疫治疗是有效的、安全的,这些免疫治疗可作为那些有高危复发风险及初始标准化疗失败的AML患者的辅助治疗。本文就近几年WT1与AML的预后及有关以WT1为靶点的主动特异性免疫治疗的研究进展予以综述。 相似文献
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An important part of fundamental research in catalysis is based on theoretical and modeling foundations which are closely connected with studies of single-crystalline catalyst surfaces. These so-called model catalysts are often prepared in the form of epitaxial thin films, and characterized using advanced material characterization techniques. This concept provides the fundamental understanding and the knowledge base needed to tailor the design of new heterogeneous catalysts with improved catalytic properties. The present contribution is devoted to development of a model catalyst system of CeO2 (ceria) on the Cu(111) substrate. We propose ways to experimentally characterize and control important parameters of the model catalyst—the coverage of the ceria layer, the influence of the Cu substrate, and the density of surface defects on ceria, particularly the density of step edges and the density and the ordering of the oxygen vacancies. The large spectrum of controlled parameters makes ceria on Cu(111) an interesting alternative to a more common model system ceria on Ru(0001) that has served numerous catalysis studies, mainly as a support for metal clusters. 相似文献