Emerging modes-of-action in drug discovery
An increasing focus on complex biology to cure diseases rather than merely treat symptoms has transformed how drug discovery can be approached. Instead of activating or blocking protein function, a growing repertoire of drug modalities can be leveraged or engineered to hijack cellular processes, suc...
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| Published in | MedChemComm Vol. 1; no. 9; pp. 155 - 1568 |
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| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
Cambridge
Royal Society of Chemistry
18.09.2019
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| Subjects | |
| Online Access | Get full text |
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| Summary: | An increasing focus on complex biology to cure diseases rather than merely treat symptoms has transformed how drug discovery can be approached. Instead of activating or blocking protein function, a growing repertoire of drug modalities can be leveraged or engineered to hijack cellular processes, such as translational regulation or degradation mechanisms. Drug hunters can therefore access a wider arsenal of modes-of-action to modulate biological processes and this review summarises these emerging strategies by highlighting the most representative examples of these approaches.
An increasing focus on complex biology to cure diseases rather than merely treat symptoms is transforming how drug discovery can be approached, and expands the arsenal of drug modalities and modes-of-actions that can be leveraged to modify diseases. |
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| Bibliography: | Dr. Frank Narjes is currently Senior Principal Scientist in the Department of Medicinal Chemistry at AstraZeneca, Sweden and Project Leader for early targets in the Respiratory, Inflammation and Autoimmunity area. His current work in AstraZeneca focusses on 'new modalities' such as bicyclic peptides and heterobifunctional degraders. Prior to joining AstraZeneca, he was employed at Merck, Sharp & Dohme in Rome, where he explored protease and polymerase inhibitors for the treatment of Hepatitis C virus infection. Frank studied chemistry at the University of Hamburg, followed by postdoctoral studies at UC Irvine. Christian Ottmann is Associate Professor at Eindhoven University of Technology, The Netherlands. He works on stabilization of 14-3-3 adapter protein PPIs by small molecules. He is coordinator of the FP7 Industry-Academia Partnership and Pathways (IAPP) 14-3-3STABS and the Horizon2020 European Training Network (ETN) TASPPI. Before taking up his current position in Eindhoven he was a group leader at the Chemical Genomics Centre (CGC) in Dortmund, Germany. In 2012 he was recipient of the Innovation Award in Medicinal/Pharmaceutical Chemistry of the GDCh/DPhG and in 2013 of the Young Chemical Biology Award of the International Chemical Biology Society (ICBS). Eric Valeur has over 15 years drug discovery experience gained at Merck, Novartis, and most recently AstraZeneca. He has led medicinal chemistry teams across several therapeutic areas and across modalities, including small molecules, macrocycles, peptides, oligonucleotides, drug conjugates, and PROTACs, delivering clinical candidates and novel technologies. He is passionate about challenging targets and disruptive drug discovery, in particular in combination with novel biology. Eric is coauthor/coinventor of over 50 publications, patents, posters, and oral presentations and holds a Ph.D. from the University of Edinburgh (under supervision of Prof. Mark Bradley) and an MBA from Imperial College London. Dr. Alleyn Plowright obtained his PhD in organic chemistry with Professor Gerald Pattenden at the University of Nottingham in 1999, and continued with postdoctoral studies with Professor Andrew Myers at Harvard University. In 2002, Alleyn joined AstraZeneca in the UK as a Medicinal Chemist before moving to AstraZeneca Sweden in 2008. In 2017 Alleyn moved to Sanofi as Head Integrated Drug Discovery Germany leading a cross-disciplinary research unit driving projects from target validation through to pre-clinical development. His current research interests include Drug Design, Phenotypic Drug Discovery and the use of diverse chemical modalities to treat metabolic, cardiovascular, immunological and rare diseases. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 ObjectType-Review-3 content type line 23 |
| ISSN: | 2040-2503 2040-2511 2040-2511 |
| DOI: | 10.1039/c9md00263d |