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2018 - Pharmacological characterization of an amino acid transporter and his bacterial homologue – a case study using the SURFE²R 96SE technology

Icon 96SE   SURFE²R 96SE Oral Presentation Video

Presenter: 
Dr. Thomas Licher, Head of in vitro Biology & High-Throughput Chemistry, Sanofi, IDD Frankfurt, Germany
Thomas made his PhD at the Center for Molecular Neurobiology in the group of Prof. Dr. Pongs on an HTS-technology for ion channel-modulating substances in 2002. He started to work for Sanofi-Aventis, later Sanofi as Post-doc, lab head and group leader in the field for Cardiac Safety and Lead Identification Technologies. Today, Thomas is Head of in vitro Biology & High-Throughput Chemistry at Sanofi in Frankfurt, Germany.

Source:
Webinar: "The SURFE²R Technology: Assays for Pharmacological and Functional Characterization of Membrane Transporters"
January 30, 2018


Abstract:

Ion channels and membrane transporters are involved in multiple (patho)physiological processes and are recognized as a growing therapeutic target class. Analysis of these proteins is challenging because of the limited availability of proper assays for efficient compound screening.
The IDD in vitro biology department in Frankfurt has a long tradition of transporter drug discovery. We apply a comprehensive repertory to identify new small molecules to modulate transporter function, resulting in several successful applications in lead optimization.
For a Na+-dependent amino-acid transporter, a recent target of Sanofi, no direct assays for pharmacological characterization were available. This target is important in two indications relevant for Sanofi and a screening cascade for identification of small molecule inhibitors was established. The Sanofi compound library was screened with a fluorescence-based membrane potential assay and actives were validated with a MS-based substrate flux assay. To validate the hits an electrophysiological assay was required. We evaluated the SURFE²R 96SE workstation, as a solid supported membrane (SSM) based electrophysiological technique, to assess transporter activity. We established an assay for automated direct recording of transporter mediated currents and successfully integrated the SURFE²R technology into the screening tree for hit validation.

 

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