Assay and drug development technologies最新文献_第10页

Developmental Cardiotoxicity and Hepatotoxicity of Flurbiprofen Axetil to Zebrafish Embryo. 氟比洛芬酯对斑马鱼胚胎的发育性心脏毒性和肝毒性。

IF 1.8 4区医学

Assay and drug development technologies Pub Date : 2022-04-01 DOI: 10.1089/adt.2021.127

Yuping Wang, Min Zhou, Jing Wang, Chu-Fang Lin, Xiang-li Gao, Li Zhang, Wenshui Yao, Longxin Zhang

{"title":"Developmental Cardiotoxicity and Hepatotoxicity of Flurbiprofen Axetil to Zebrafish Embryo.","authors":"Yuping Wang, Min Zhou, Jing Wang, Chu-Fang Lin, Xiang-li Gao, Li Zhang, Wenshui Yao, Longxin Zhang","doi":"10.1089/adt.2021.127","DOIUrl":"https://doi.org/10.1089/adt.2021.127","url":null,"abstract":"Flurbiprofen axetil (FA) is a nonsteroidal targeted analgesic and widely used for postoperative analgesia and cancer analgesia. Extensive works have been done in the evaluation of FA's clinical analgesic effect on adults. Along with the increase of FA usage, the potential toxicity and molecular mechanism in embryo development need to be better understood. In this article, multiple embryonic development indexes of zebrafish were introduced to evaluate the FA toxicity to provide clinical guidance for gravidas medicine. We performed a zebrafish embryo toxicity (ZFET) test by exposing embryos to a series of concentration gradients of FA medium starting from 24 hours postfertilization (hpf). The mortality rate, hatching rate, and malformation rate of drug-treated zebrafish were assessed at 72, 96, and 120 hpf. Effects of ≤10% lethal concentration (LC10) of FA on embryogenesis were evaluated by eye area, body length, and yolk sac area. A 0.5 μg/mL or fewer FA treatment did not show any adverse effects, but the LC10 FA significantly caused zebrafish malformation. Organ disorders, including slow heart rate, enlarged pericardium, and liver atrophy, were found in the dysplasia individuals when compared with control. TUNEL assay suggested that apoptotic cells in malformation embryos were produced by FA and the increasing dosage exacerbated apoptosis. Quantitative real-time polymerase chain reaction revealed that expressions of cardiac development-associated transcription factors, liver development-related genes, and apoptosis regulating genes were aberrant. These results indicate that the ZFET can be applied in the FA toxicity test, and a low lethal dose of FA is harmful to zebrafish embryogenesis, especially in embryo carcinogenesis and hepatogenesis.","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42987879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Development of a High-Throughput Screening Assay for Small-Molecule Inhibitors of Androgen Receptor Splice Variants. 雄激素受体剪接变异体小分子抑制剂高通量筛选试验的建立。

IF 1.8 4区医学

Assay and drug development technologies Pub Date : 2022-04-01 Epub Date: 2022-03-23 DOI: 10.1089/adt.2021.128

Amy E Monaghan, Alison Porter, Irene Hunter, Angus Morrison, Stuart P McElroy, Iain J McEwan

{"title":"Development of a High-Throughput Screening Assay for Small-Molecule Inhibitors of Androgen Receptor Splice Variants.","authors":"Amy E Monaghan, Alison Porter, Irene Hunter, Angus Morrison, Stuart P McElroy, Iain J McEwan","doi":"10.1089/adt.2021.128","DOIUrl":"https://doi.org/10.1089/adt.2021.128","url":null,"abstract":"The role of the androgen receptor (AR) in the progression of prostate cancer (PCa) is well established and competitive inhibition of AR ligand binding domain (LBD) has been the mainstay of antiandrogen therapies for advanced and metastatic disease. However, the efficacy of such drugs is often limited by the emergence of resistance, mediated through point mutations and receptor splice variants lacking the AR-LBD. As a result, the prognosis for patients with malignant, castrate-resistant disease remains poor. The amino terminal domain (NTD) of the AR has been shown to be critical for AR function. Its modular activation function (AF-1) is important for both gene regulation and participation in protein-protein interactions. However, due to the intrinsically disordered structure of the domain, its potential as a candidate for therapeutic intervention has been generally overlooked. In this article, we describe the design and development of a functional cell-based assay aimed at identifying small-molecule inhibitors of the AR-NTD. We demonstrate the suitability of the assay for high-throughput screening platforms and validate two initial hits emerging from a small, targeted, library screen in PCa cells.","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cb/b5/adt.2021.128.PMC9057896.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40328156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Call for Special Issue Papers: Chemical Probes and Pharmacological Tools for Imaging Applications. 特刊论文征集：用于成像应用的化学探针和药理学工具。

IF 1.8 4区医学

Assay and drug development technologies Pub Date : 2022-04-01 DOI: 10.1089/adt.2022.29099.cfp

M. Kostic, B. Melancon

引用次数: 0

Interview with Craig W. Lindsley, PhD. Craig W. Lindsley博士访谈

IF 1.8 4区医学

Assay and drug development technologies Pub Date : 2022-03-31 DOI: 10.1089/adt.2022.29097.bjm

B. Melancon

引用次数: 0

Forging Ahead with ASSAY. 与化验携手前行。

IF 1.8 4区医学

Assay and drug development technologies Pub Date : 2022-03-30 DOI: 10.1089/adt.2022.29100.bjm

B. Melancon

引用次数: 0

Drug Repurposing Patent Applications October: December 2021. 药物再利用专利申请10月:2021年12月

IF 1.8 4区医学

Assay and drug development technologies Pub Date : 2022-02-09 DOI: 10.1089/adt.2022.002

H. Mucke

引用次数: 0

Call for Special Issue Papers: Chemical Probes and Pharmacological Tools for Kinase Signaling. 特刊论文征集：激酶信号传导的化学探针和药理学工具。

IF 1.8 4区医学

Assay and drug development technologies Pub Date : 2022-02-03 DOI: 10.1089/adt.2020.29096.cfp5

Milka Kostic, Bruce J Melancon

引用次数: 0

Call for Special Issue Papers: Special Issue on High-throughput Technologies for the Discovery and Development of Chemical Probes and Pharmacological Tools. 特刊论文征集:化学探针和药理学工具的高通量发现和开发技术特刊。

IF 1.8 4区医学

Assay and drug development technologies Pub Date : 2022-02-03 DOI: 10.1089/adt.2020.29095.cfp5

Milka Kostic, Bruce J Melancon

引用次数: 0

A New Spectral Shift-Based Method to Characterize Molecular Interactions. 一种新的基于光谱位移的分子相互作用表征方法。

IF 1.8 4区医学

Assay and drug development technologies Pub Date : 2022-02-01 Epub Date: 2022-02-15 DOI: 10.1089/adt.2021.133

Andreas Langer, Tanja Bartoschik, Ondrej Cehlar, Stefan Duhr, Philipp Baaske, Werner Streicher

{"title":"A New Spectral Shift-Based Method to Characterize Molecular Interactions.","authors":"Andreas Langer, Tanja Bartoschik, Ondrej Cehlar, Stefan Duhr, Philipp Baaske, Werner Streicher","doi":"10.1089/adt.2021.133","DOIUrl":"https://doi.org/10.1089/adt.2021.133","url":null,"abstract":"There are many fluorescence-based applications that can be used to characterize molecular interactions. However, available methods often depend on site-specific labeling techniques or binding-induced changes in conformation or size of the probed target molecule. To overcome these limitations, we applied a ratiometric dual-emission approach that quantifies ligand-induced spectral shifts with sub-nanometer sensitivity. The use of environment-sensitive near-infrared dyes with the method we describe enables affinity measurements and thermodynamic characterization without the explicit need for site-specific labeling or ligand-induced conformational changes. We demonstrate that in-solution spectral shift measurements enable precise characterization of molecular interactions for a variety of biomolecules, including proteins, antibodies, and nucleic acids. Thereby, the described method is not limited to a subset of molecules since even the most challenging samples of research and drug discovery projects like membrane proteins and intrinsically disordered proteins can be analyzed.","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39928366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Automated Assays to Identify Modulators of Transcription Factor EB Translocation and Autophagy. 鉴定转录因子EB易位和自噬调节剂的自动测定。

IF 1.8 4区医学

Assay and drug development technologies Pub Date : 2022-02-01 Epub Date: 2021-12-13 DOI: 10.1089/adt.2021.119

Anaelle da Costa, Christèle Picoli, Franck Mouthon, Mathieu Charvériat

{"title":"Automated Assays to Identify Modulators of Transcription Factor EB Translocation and Autophagy.","authors":"Anaelle da Costa, Christèle Picoli, Franck Mouthon, Mathieu Charvériat","doi":"10.1089/adt.2021.119","DOIUrl":"https://doi.org/10.1089/adt.2021.119","url":null,"abstract":"Autophagy is a process leading to the degradation of cellular material, in organelles called lysosomes, to supply energy or generate building blocks for the synthesis of new materials. Over the past decades, its role has been evidenced in several indications, notably in neurodegenerative disorders and orphan diseases called lysosomal storage disorders and its modulation is largely envisioned as a therapeutic avenue to alleviate the symptoms and reverse the clinical courses of these indications. Identifying new chemical classes and drugs is, hence, of huge importance. In this study, we developed automated assays to assess the potential efficacy of chemical compounds on different steps of autophagy, notably its induction through the localization of a largely involved transcription factor, transcription factor EB (TFEB). These assays were then used to screen a collection of 1,520 approved drugs. This study led to the identification of five candidate hits modulating autophagy and TFEB subcellular localization. Our results suggest the repurposing potential of already approved drugs in central nervous system disorders with lysosomal storage impairments.","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39718086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1