OCT 23, 2018 7:00 AM PDT

FLIPR 1536-well application in high throughput screening

Sponsored by: Molecular Devices
Speakers

Abstract

DATE: October 23, 2018
TIME: 7:00AM PDT
10:00AM EDT, 3:00PM BST, 4:00PM CET

Over the past five years, over 70 high-throughput screening campaigns have been performed at Pivot Park Screening Centre (PPSC) for the European Lead Factory (ELF).  These HTS campaigns have been executed on a compound library that has grown from 320,000 to 450,000 compounds.

The screens cover a wide range of target classes, including more demanding cellular targets like ion channels and protein-protein interactions. As an example of one of the ELF screening campaigns, we will present the results of a high-throughput screening to identify selective agonists for an ion channel using the Molecular Devices FLIPR Tetra® High-Throughput Cellular Screening System.

In this project, the assay was based on stable cell lines expressing the ion channel. The assay was successfully miniaturized to 1536 well format using a standard Molecular Devices membrane potential dye. The screening cascade will be presented.

Another highly important aspect for effective drug development is the assessment of cardiac safety and efficacy of drug candidates. Hence, there is a pressing need for in vitro screening methods to detect cardioactive effects of compounds early in the drug discovery process. To provide a relevant in vitro model to investigate effects of drug candidates on cardiac physiology, we have evaluated hiPSC-derived ventricular cardiomyocytes (Pluricyte® Cardiomyocytes), which exhibit a relatively high level of maturity. We used these cardiomyocytes in combination with a fluorescent calcium dye (FLIPR Calcium 6 Assay Kit, Molecular Devices) to develop a high-throughput drug screening assay on the FLIPR Tetra® (Molecular Devices) screening platform.

After optimization of the assay for application with 384-well plates, we investigated the impact of different cardioactive compounds (e.g. hERG-channel blockers, calcium channel agonists/antagonists and β-adrenergic agonists) on the calcium transients in Pluricyte® Cardiomyocytes. 

Learning objectives:

  • Using full automation to perform complex GPCR testing
  • Tips and tricks for 1536-well FLIPR screening
  • Calcium kinetics in cardiac safety testing

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OCT 23, 2018 7:00 AM PDT

FLIPR 1536-well application in high throughput screening

Sponsored by: Molecular Devices


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