Journal
NATURE REVIEWS DRUG DISCOVERY
Volume 21, Issue 2, Pages 115-140Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41573-021-00320-3
Keywords
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Funding
- Medical Research Council (MRC) [MR/V028669/1, MR/R009120/1]
- Engineering and Physical Sciences Research Council (EPSRC) [EP/R03558X/1]
- British Lung Foundation (BLF) [MEDPG21F\4]
- National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre [BRC-121520014]
- Royal Papworth Hospital
- Alpha1-Foundation [830153, 614939]
- Wellcome Trust Principal Research Fellowship (Wellcome) [200848/Z/16/Z]
- Wellcome Trust Strategic Award [100140]
- MRC [MR/V028669/1] Funding Source: UKRI
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Research on drug-like molecules targeting ER stress and UPR has made progress, but limitations still exist. Understanding these limitations is crucial for the development of these molecules into therapeutic drugs.
The accumulation of misfolded proteins in the endoplasmic reticulum (ER) leads to ER stress, resulting in activation of the unfolded protein response (UPR) that aims to restore protein homeostasis. However, the UPR also plays an important pathological role in many diseases, including metabolic disorders, cancer and neurological disorders. Over the last decade, significant effort has been invested in targeting signalling proteins involved in the UPR and an array of drug-like molecules is now available. However, these molecules have limitations, the understanding of which is crucial for their development into therapies. Here, we critically review the existing ER stress and UPR-directed drug-like molecules, highlighting both their value and their limitations.
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