Transporter Assays Using Solid Supported Membranes: A Novel Screening Platform for Drug Discovery

2006 ◽  
Vol 4 (5) ◽  
pp. 575-582 ◽  
Author(s):  
Bela Kelety ◽  
Kerstin Diekert ◽  
Joanna Tobien ◽  
Natalie Watzke ◽  
Wolfgang Dörner ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Supported Membranes ◽  
Screening Platform ◽  
Solid Supported Membranes

Phosphorylation of C-terminal polycystin-2 influences the interaction with PIGEA14: A QCM study based on solid supported membranes

2013 ◽  
Vol 437 (4) ◽  
pp. 532-537 ◽  
Author(s):  
Daniela Morick ◽  
Michaela Schatz ◽  
Raphael Hubrich ◽  
Helen Hoffmeister ◽  
Anya Krefft ◽  
...  
Keyword(s):  
Supported Membranes ◽  
Solid Supported Membranes

scholarly journals High-Content Phenotypic Profiling in Esophageal Adenocarcinoma Identifies Selectively Active Pharmacological Classes of Drugs for Repurposing and Chemical Starting Points for Novel Drug Discovery

2020 ◽  
Vol 25 (7) ◽  
pp. 770-782 ◽  
Author(s):  
Rebecca E. Hughes ◽  
Richard J. R. Elliott ◽  
Alison F. Munro ◽  
Ashraff Makda ◽  
J. Robert O’Neill ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Esophageal Adenocarcinoma ◽  
Cell Lines ◽  
Cancer Biology ◽  
Large Scale ◽  
Chemical Library ◽  
Screening Platform ◽  
Poor Outcomes ◽  
Cell Phenotypes ◽  
Selective Activity

Esophageal adenocarcinoma (EAC) is a highly heterogeneous disease, dominated by large-scale genomic rearrangements and copy number alterations. Such characteristics have hampered conventional target-directed drug discovery and personalized medicine strategies, contributing to poor outcomes for patients. We describe the application of a high-content Cell Painting assay to profile the phenotypic response of 19,555 compounds across a panel of six EAC cell lines and two tissue-matched control lines. We built an automated high-content image analysis pipeline to identify compounds that selectively modified the phenotype of EAC cell lines. We further trained a machine-learning model to predict the mechanism of action of EAC selective compounds using phenotypic fingerprints from a library of reference compounds. We identified a number of phenotypic clusters enriched with similar pharmacological classes, including methotrexate and three other antimetabolites that are highly selective for EAC cell lines. We further identify a small number of hits from our diverse chemical library that show potent and selective activity for EAC cell lines and that do not cluster with the reference library of compounds, indicating they may be selectively targeting novel esophageal cancer biology. Overall, our results demonstrate that our EAC phenotypic screening platform can identify existing pharmacologic classes and novel compounds with selective activity for EAC cell phenotypes.

scholarly journals UsingDrosophilaas a platform for drug discovery from natural products in Parkinson's disease

MedChemComm ◽  
2019 ◽  
Vol 10 (6) ◽  
pp. 867-879 ◽  
Author(s):  
Urmila Maitra ◽  
Lukasz Ciesla
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Natural Products ◽  
Drug Discovery ◽  
Therapeutic Potential ◽  
Natural Extracts ◽  
New Drug ◽  
Screening Platform ◽  
Drug Leads

The review provides an overview of discovery of new drug leads from natural extracts usingDrosophilaas a screening platform to evaluate the therapeutic potential of phytochemicals against Parkinson's disease.

scholarly journals Measuring Ion Channels on Solid Supported Membranes

2009 ◽  
Vol 97 (1) ◽  
pp. 388-396 ◽  
Author(s):  
Patrick Schulz ◽  
Benjamin Dueck ◽  
Alexandre Mourot ◽  
Lina Hatahet ◽  
Klaus Fendler
Keyword(s):  
Ion Channels ◽  
Supported Membranes ◽  
Solid Supported Membranes

Robust Electrophysiological Assays using Solid Supported Membranes: the Organic Cation Transporter OCT2

2011 ◽  
Vol 64 (1) ◽  
pp. 31 ◽  
Author(s):  
Olga Gaiko ◽  
Ingo Janausch ◽  
Sven Geibel ◽  
Henning Vollert ◽  
Petra Arndt ◽  
...  
Keyword(s):  
Cell Lines ◽  
Organic Cation ◽  
Chinese Hamster ◽  
Organic Cation Transporter ◽  
Supported Membranes ◽  
Cho Cell ◽  
Drug Candidates ◽  
Substrate Affinities ◽  
Solid Supported Membranes

An electrophysiological assay platform based on solid supported membranes (SSM) for the organic cation transporter (OCT) is presented. Stable Chinese hamster ovary (CHO) cell lines overexpressing the human (hOCT2) and rat transporters (rOCT2) were generated and validated. Membrane preparations from the cell lines were investigated using SSM-based electrophysiology. Baculovirus transfected insect cells (HighFive and Mimic Sf9) were also tested with the same assay but yielded less than optimal results. The assays were validated by the determination of substrate affinities and inhibition by standard inhibitors. The study demonstrates the suitability of the SSM-based electrophysiological OCT assay for rapid and automatic screening of drug candidates.

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