title: New Modalities for Challenging Targets in Drug Discovery.
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.
authors.affiliation: Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Pepparedsleden 1, Mölndal, 431 83, Sweden.
authors.forename: Eric
authors.initials: E
authors.lastname: Valeur
authors.affiliation: Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Pepparedsleden 1, Mölndal, 431 83, Sweden.|AstraZeneca MPI Satellite Unit, Abteilung Chemische Biologie, Max Planck Institut für Molekulare Physiologie, Dortmund, Germany.
authors.forename: Stéphanie M
authors.initials: SM
authors.lastname: Guéret
authors.affiliation: Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Pepparedsleden 1, Mölndal, 431 83, Sweden.|AstraZeneca MPI Satellite Unit, Abteilung Chemische Biologie, Max Planck Institut für Molekulare Physiologie, Dortmund, Germany.
authors.forename: Hélène
authors.initials: H
authors.lastname: Adihou
authors.affiliation: Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Pepparedsleden 1, Mölndal, 431 83, Sweden.|AstraZeneca MPI Satellite Unit, Abteilung Chemische Biologie, Max Planck Institut für Molekulare Physiologie, Dortmund, Germany.
authors.forename: Ranganath
authors.initials: R
authors.lastname: Gopalakrishnan
authors.affiliation: Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Pepparedsleden 1, Mölndal, 431 83, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Lemurell
authors.affiliation: Abteilung Chemische Biologie, Max Planck Institut für Molekulare Physiologie, Dortmund, Germany.|Fakultät für Chemie und Chemische Biologie, Technische Universität Dortmund, Germany.
authors.forename: Herbert
authors.initials: H
authors.lastname: Waldmann
authors.affiliation: Chemical Genomics Centre of the Max Planck Society, Dortmund, Germany.|Department of Chemistry & Pharmaceutical Sciences, VU University Amsterdam, The Netherlands.
authors.forename: Tom N
authors.initials: TN
authors.lastname: Grossmann
authors.affiliation: Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Pepparedsleden 1, Mölndal, 431 83, Sweden.
authors.forename: Alleyn T
authors.initials: AT
authors.lastname: Plowright
mesh_terms: D055808:Drug Discovery; D006801:Humans; D009696:Nucleic Acids / Q000037:antagonists & inhibitors* / Q000737:chemistry; D009841:Oligonucleotides / Q000737:chemistry / Q000494:pharmacology*; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D013499:Surface Properties
chemical_list: D009696:Nucleic Acids; D009841:Oligonucleotides; D011506:Proteins; D054852:Small Molecule Libraries
keywords: drug conjugates; macrocycles; oligonucleotides; peptides