Synthesis and biological evaluation of cyclobutane-based β3 integrin antagonists: A novel approach to targeting integrins for cancer therapy

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Publication date
2023-08Author
Sutherland, Mark
Gordon, Andrew
Al-Shammari, F.O.F.O.
Throup, Adam E.
La Corte, A.C.
Philippou, H.
Shnyder, Steven

Patterson, Laurence H.
Sheldrake, Helen M.
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© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Peer-Reviewed
YesOpen Access status
openAccessAccepted for publication
2023-08-06
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Show full item recordAbstract
The Arg-Gly-Asp (RGD)-binding family of integrin receptors, and notably the β3 subfamily, are key to multiple physiological processes involved in tissue development, cancer proliferation, and metastatic dissemination. While there is compelling preclinical evidence that both αvβ3 and αIIbβ3 are important anticancer targets, most integrin antagonists developed to target the β3 integrins are highly selective for αvβ3 or αIIbβ3. We report the design, synthesis, and biological evaluation of a new structural class of ligand-mimetic β3 integrin antagonist. These new antagonists combine a high activity against αvβ3 with a moderate affinity for αIIbβ3, providing the first evidence for a new approach to integrin targeting in cancer.Version
Published versionCitation
Sutherland M, Gordon A, Al-Shammari FOFO et al (2023) Synthesis and biological evaluation of cyclobutane-based β3 integrin antagonists: A novel approach to targeting integrins for cancer therapy. Cancers. 15(16): 4023.Link to Version of Record
https://doi.org/10.3390/cancers15164023Type
Articleae974a485f413a2113503eed53cd6c53
https://doi.org/10.3390/cancers15164023