New Modalities for Challenging Targets in Drug Discovery. Issue 35 (24th July 2017)

• Record Type: Journal Article
• Authors: Valeur, Eric; Guéret, Stéphanie M.; Adihou, Hélène; Gopalakrishnan, Ranganath; Lemurell, Malin; Waldmann, Herbert; Grossmann, Tom N.; Plowright, Alleyn T.
• Is Part Of: Angewandte Chemie international edition. Volume 56:Issue 35(2017)
• Page Start: 10294
• Page End: 10323
• Publication Date: 2017-07-24
• Subjects: drug conjugates -- macrocycles -- oligonucleotides -- peptides; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201611914
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Our ever‐increasing understanding of biological systems is providing a range of exciting novel biological targets, whose modulation may enable novel therapeutic options for many diseases. These targets include protein–protein and protein–nucleic acid interactions, which are, however, often refractory to classical small‐molecule approaches. Other types of molecules, or modalities, are therefore required to address these targets, which has led several academic research groups and pharmaceutical companies to increasingly use the concept of so‐called "new modalities". This Review defines for the first time the scope of this term, which includes novel peptidic scaffolds, oligonucleotides, hybrids, molecular conjugates, as well as new uses of classical small molecules. We provide the most representative examples of these modalities to target large binding surface areas such as those found in protein–protein interactions and for biological processes at the center of cell regulation. Abstract : Out of the box : A new generation of molecules, including novel peptides, oligonucleotides, hybrids, and molecular conjugates, is enabling novel strategies to address challenging targets and biological processes at the center of cell regulation. This Review defines these "new modalities", and highlights how progress in this area is now leading to a range of novel drug candidates.