Wu, Z, Suppo, J-S, Tumova, S et al. (10 more authors) (2020) Bridgehead Modifications of Englerin A Reduce TRPC4 Activity and Intravenous Toxicity but not Cell Growth Inhibition. ACS Medicinal Chemistry Letters, 11 (9). pp. 1711-1716. ISSN 1948-5875
Abstract
Modifications at the bridgehead position of englerin A were made to explore the effects of variation at this site on the molecule for biological activity, as judged by the NCI 60 screen, in which englerin A is highly potent and selective for renal cancer cells. Replacement of the isopropyl group by other, larger substituents yielded compounds which displayed excellent selectivity and potency comparable to the natural product. Selected compounds were also evaluated for their effect on the ion channel TRPC4 as well as for intravenous toxicity in mice, and these had lower potency in both assays compared to englerin A.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 American Chemical Society. This is an author produced version of an article published in ACS Medicinal Chemistry Letters. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Englerin; kidney cancer; ion channels; TRPC4; mice |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) |
Funding Information: | Funder Grant number MRC (Medical Research Council) MC_PC_17165 |
Depositing User: | Symplectic Publications |
Date Deposited: | 01 Oct 2020 13:14 |
Last Modified: | 03 Aug 2021 00:38 |
Status: | Published |
Publisher: | American Chemical Society |
Identification Number: | 10.1021/acsmedchemlett.0c00186 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:166143 |