Pharmacological targeting of IRE1 in cancer
IRE1α (inositol requiring enzyme 1 alpha) is one of the main transducers of the unfolded protein response (UPR). IRE1α plays instrumental protumoral roles in several cancers, and high IRE1α activity has been associated with poorer prognoses. In this context, IRE1α has been identified as a potentiall...
| Main Authors: | , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Cell Press
2020
|
| _version_ | 1797060884659437568 |
|---|---|
| author | Pelizzari Raymundo, D Doultsinos, D Guillory, X Carlesso, A Eriksson, LA Chevet, E |
| author_facet | Pelizzari Raymundo, D Doultsinos, D Guillory, X Carlesso, A Eriksson, LA Chevet, E |
| author_sort | Pelizzari Raymundo, D |
| collection | OXFORD |
| description | IRE1α (inositol requiring enzyme 1 alpha) is one of the main transducers of the unfolded protein response (UPR). IRE1α plays instrumental protumoral roles in several cancers, and high IRE1α activity has been associated with poorer prognoses. In this context, IRE1α has been identified as a potentially relevant therapeutic target. Pharmacological inhibition of IRE1α activity can be achieved by targeting either the kinase domain or the RNase domain. Herein, the recent advances in IRE1α pharmacological targeting is summarized. We describe the identification and optimization of IRE1α inhibitors as well as their mode of action and limitations as anticancer drugs. The potential pitfalls and challenges that could be faced in the clinic, and the opportunities that IRE1α modulating strategies may present are discussed. |
| first_indexed | 2024-03-06T20:23:15Z |
| format | Journal article |
| id | oxford-uuid:2e8a9876-83af-40e2-9f45-02639d2e6cdc |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:23:15Z |
| publishDate | 2020 |
| publisher | Cell Press |
| record_format | dspace |
| spelling | oxford-uuid:2e8a9876-83af-40e2-9f45-02639d2e6cdc2022-03-26T12:49:36ZPharmacological targeting of IRE1 in cancerJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2e8a9876-83af-40e2-9f45-02639d2e6cdcEnglishSymplectic ElementsCell Press2020Pelizzari Raymundo, DDoultsinos, DGuillory, XCarlesso, AEriksson, LAChevet, EIRE1α (inositol requiring enzyme 1 alpha) is one of the main transducers of the unfolded protein response (UPR). IRE1α plays instrumental protumoral roles in several cancers, and high IRE1α activity has been associated with poorer prognoses. In this context, IRE1α has been identified as a potentially relevant therapeutic target. Pharmacological inhibition of IRE1α activity can be achieved by targeting either the kinase domain or the RNase domain. Herein, the recent advances in IRE1α pharmacological targeting is summarized. We describe the identification and optimization of IRE1α inhibitors as well as their mode of action and limitations as anticancer drugs. The potential pitfalls and challenges that could be faced in the clinic, and the opportunities that IRE1α modulating strategies may present are discussed. |
| spellingShingle | Pelizzari Raymundo, D Doultsinos, D Guillory, X Carlesso, A Eriksson, LA Chevet, E Pharmacological targeting of IRE1 in cancer |
| title | Pharmacological targeting of IRE1 in cancer |
| title_full | Pharmacological targeting of IRE1 in cancer |
| title_fullStr | Pharmacological targeting of IRE1 in cancer |
| title_full_unstemmed | Pharmacological targeting of IRE1 in cancer |
| title_short | Pharmacological targeting of IRE1 in cancer |
| title_sort | pharmacological targeting of ire1 in cancer |
| work_keys_str_mv | AT pelizzariraymundod pharmacologicaltargetingofire1incancer AT doultsinosd pharmacologicaltargetingofire1incancer AT guilloryx pharmacologicaltargetingofire1incancer AT carlessoa pharmacologicaltargetingofire1incancer AT erikssonla pharmacologicaltargetingofire1incancer AT chevete pharmacologicaltargetingofire1incancer |