p97: An Emerging Target for Cancer, Neurodegenerative Diseases, and Viral Infections
| Autor: | David J P Kornfilt, Peter Wipf, Donna M. Huryn |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Cellular homeostasis
Endoplasmic-reticulum-associated protein degradation medicine.disease_cause Endoplasmic Reticulum 01 natural sciences Protein Structure Secondary 03 medical and health sciences Drug Delivery Systems Valosin Containing Protein Neoplasms Drug Discovery medicine Animals Humans Benzothiazoles 030304 developmental biology 0303 health sciences Chemistry Autophagy Neurodegeneration Wild type Cancer Cytomegalovirus Neurodegenerative Diseases medicine.disease Virology 0104 chemical sciences Protein Structure Tertiary 010404 medicinal & biomolecular chemistry Herpes simplex virus Virus Diseases Molecular Medicine Acetanilides Protein Binding |
| Zdroj: | Journal of medicinal chemistry. 63(5) |
| ISSN: | 1520-4804 |
| Popis: | The AAA+ ATPase, p97, also referred to as VCP, plays an essential role in cellular homeostasis by regulating endoplasmic reticulum-associated degradation (ERAD), mitochondrial-associated degradation (MAD), chromatin-associated degradation, autophagy, and endosomal trafficking. Mutations in p97 have been linked to a number of neurodegenerative diseases, and overexpression of wild type p97 is observed in numerous cancers. Furthermore, p97 activity has been shown to be essential for the replication of certain viruses, including poliovirus, herpes simplex virus (HSV), cytomegalovirus (CMV), and influenza. Taken together, these observations highlight the potential for targeting p97 as a therapeutic approach in neurodegeneration, cancer, and certain infectious diseases. This Perspective reviews recent advances in the discovery of small molecule inhibitors of p97, their optimization and characterization, and therapeutic potential. |
| Databáze: | OpenAIRE |
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