Special Issue "Drug Discovery Tools"

Guest Editor
Dr. Andreas Vogt
Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA
Website: http://www.pharmacology.us/Faculty.aspx?FacultyID=109
E-Mail: avogt@pitt.edu
Interests: drug discovery, high-content screening, zebrafish, cancer, phosphatases

Dear Colleagues,

Over the last two decades, drug discovery has evolved into a science of its own. Advances in genomics, proteomics, chemical library synthesis, and assay technologies have firmly established high-throughput screening in both industry and academia. This special issue captures and highlights advances, successes, and challenges of contemporary drug discovery. We invite articles on all aspects of drug discovery tool development and utilization, including but not limited to, assay technologies, assay design and optimization, model systems (yeast, cells, worms, flies, zebrafish), biosensors, molecular modeling, and virtual screening.

Andreas Vogt
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed Open Access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 500 CHF (Swiss Francs). English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.

• assay technologies
• high-throughput screening
• high-content analysis
• model systems
• molecular modeling
• virtual screening

Title: A HCS Method to Measure Bile Efflux in Collagen Overlay Cultures of Primary Rat Hepatocytes in 384 Well Microtiter Plates
Author: Lawrence A. Vernetti
Affiliation: Drug Discovery institute, University of Pittsburgh, Pittsburgh, PA, USA
Abstract: Cholestasis, which is associated in 17 - 27% of clinically adverse condition in the liver, is not often identified in preclinical safety studies.   Drugs can induce one form of intra-hepatic cholestasis by inhibiting the Bile Salt Exporter Protein (BSEP) and multi-drug resistance-associated protein 2 (Mrp2).  These unidirectional transport proteins are located on the hepatocyte-bile canalicular surface and serve to pump bile salts, drugs and metabolites into the bile.  The traditional assay for monitoring these proteins is a low throughput, 6 or 24 well assay using hepatocytes maintained as a 'sandwich' under collagen or Matrigel pads and measured by a two readout assay.    Here is reported a single readout, robust HCS method in 384 well microtiter plates using rat hepatocytes in collagen sandwich cultures.  The assay can be used to screen up to 16 compounds in duplicate at ten point dose response points to establish bile efflux inhibition curves.  A set of standard reference compounds of known cholestatic potential were chosen from the macrolide, tetracycline, fluoroquinolone and aminoglycoside antibiotics and from clinically used triazole and imidazole anti-fungal drugs.  The results of the compounds from this assay are shown to be in concordance with reported clinical cholestasis.