Discovery of new erbB4 inhibitors: Repositioning an orphan chemical library by inverse virtual screening.

Authors :: Giordano A
Forte G
Massimo L
Riccio R
Bifulco G
Di Micco S
Source :: European journal of medicinal chemistry [Eur J Med Chem] 2018 May 25; Vol. 152, pp. 253-263. Date of Electronic Publication: 2018 Apr 12.
Publication Year :: 2018
Abstract: Inverse Virtual Screening (IVS) is a docking based approach aimed to the evaluation of the virtual ability of a single compound to interact with a library of proteins. For the first time, we applied this methodology to a library of synthetic compounds, which proved to be inactive towards the target they were initially designed for. Trifluoromethyl-benzenesulfonamides 3-21 were repositioned by means of IVS identifying new lead compounds (14-16, 19 and 20) for the inhibition of erbB4 in the low micromolar range. Among these, compound 20 exhibited an interesting value of IC <subscript>50</subscript> on MCF7 cell lines, thus validating IVS in lead repurposing.<br /> (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Subjects :: Cell Cycle Checkpoints drug effects
Dose-Response Relationship, Drug
Humans
MCF-7 Cells
Molecular Structure
Receptor, ErbB-4 metabolism
Small Molecule Libraries chemical synthesis
Small Molecule Libraries chemistry
Structure-Activity Relationship
Sulfonamides chemical synthesis
Sulfonamides chemistry
Tumor Cells, Cultured
Benzenesulfonamides
Drug Discovery
Molecular Docking Simulation
Receptor, ErbB-4 antagonists & inhibitors
Small Molecule Libraries pharmacology
Sulfonamides pharmacology

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