Clinical candidates modulating protein-protein interactions: The fragment-based experience.

Autor: Valenti D; Medicinal Chemistry, Taros Chemicals GmbH & Co. KG, Emil-Figge-Straße 76a, 44227, Dortmund, Germany; Department of Biomedical Engineering and Institute for Complex Molecular Systems, Technische Universiteit Eindhoven, Den Dolech 2, 5612, AZ, Eindhoven, the Netherlands., Hristeva S; Medicinal Chemistry, Taros Chemicals GmbH & Co. KG, Emil-Figge-Straße 76a, 44227, Dortmund, Germany., Tzalis D; Medicinal Chemistry, Taros Chemicals GmbH & Co. KG, Emil-Figge-Straße 76a, 44227, Dortmund, Germany. Electronic address: DTzalis@taros.de., Ottmann C; Department of Biomedical Engineering and Institute for Complex Molecular Systems, Technische Universiteit Eindhoven, Den Dolech 2, 5612, AZ, Eindhoven, the Netherlands; Department of Chemistry, University of Duisburg-Essen, Universitätsstraße 7, 45117, Essen, Germany. Electronic address: C.Ottmann@tue.nl.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2019 Apr 01; Vol. 167, pp. 76-95. Date of Electronic Publication: 2019 Feb 05.
DOI: 10.1016/j.ejmech.2019.01.084
Abstrakt: Protein-protein interactions (PPIs) cover a very wide range of biological functions and consequently have become one of the favourite targets for new therapeutic strategies. PPIs are strongly characterised by an intricate and dynamic network of surface interactions occurring between two or more proteins. Because of the complexity of these interactions, many strategies have been applied with the aim to find selective modulators for a specific protein-protein complex. During the last decade, fragment-based approaches have served many drug discovery programs with an impressive increment of contributions, gaining a remarkable role in PPIs modulators' development. In this review, we detail the successful fragment-to-clinical candidate evolutions related to PPI modulation. An overview on the physico-chemical properties of both fragment hits and lead compounds will be presented together with a statistical analysis of their distribution.
(Copyright © 2019 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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