The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
Targeting the AAA ATPase p97 as an Approach to Treat Cancer through Disruption of Protein Homeostasis
Open accessAbstract
Summary p97 is a AAA-ATPase with multiple cellular functions, one of which is critical regulation of protein homeostasis pathways. We describe the characterization of CB-5083, a potent, selective and orally bioavailable inhibitor of p97. Treatment of tumor cells with CB-5083 leads to accumulation of poly-ubiquitinated proteins, retention of endoplasmic reticulum associated degradation (ERAD) substrates and generation of irresolvable proteotoxic stress leading to activation of the apoptotic arm of the unfolded protein response (UPR). In xenograft models, CB-5083 causes modulation of key p97-related pathways, induces apoptosis and has antitumor activity in a broad range of both hematological and solid tumor models. Molecular determinants of CB-5083 activity include expression of genes in the ERAD pathway providing a potential strategy for patient selection.
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Metadata
- Authors
- Anderson, D. J., Le Moigne, R., Djakovic, S., Kumar, B., Rice, J., Wong, S., Wang, J., Yao, B., Valle, E., Kiss von Soly, S., Madriaga, A., Soriano, F., Menon, M.-K., Wu, Z. Y., Kampmann, M., Chen, Y., Weissman, J. S., Aftab, B. T., Yakes, F. M., Shawver, L., Zhou, H.-J., Wustrow, D., & Rolfe, M.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2015-11
- Volume
- 28
- Issue
- 5
- Pages
- 653-665
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2156739666
- Cited by
- 389
- References
- 55
- FWCI
- 12.99
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Anderson, D. J., Le Moigne, R., Djakovic, S., Kumar, B., Rice, J., Wong, S., Wang, J., Yao, B., Valle, E., Kiss von Soly, S., Madriaga, A., Soriano, F., Menon, M.-K., Wu, Z. Y., Kampmann, M., Chen, Y., Weissman, J. S., Aftab, B. T., Yakes, F. M., . . . Rolfe, M. (2015). Targeting the AAA ATPase p97 as an Approach to Treat Cancer through Disruption of Protein Homeostasis. Cancer Cell. https://doi.org/10.1016/j.ccell.2015.10.002
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
