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Synthesis and PI3 Kinase Inhibition Activity of a Wortmannin-Leucine Derivative

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title
Synthesis and PI3 Kinase Inhibition Activity of a Wortmannin-Leucine Derivative
author
Cantrell, W.
author
Huang, Y.
author
Menchaca, A.
author
Kulik, G.
abstract
Wortmannin is a potent covalent inhibitor of PI3K that shows substantial in vivo toxicity and thus is unsuitable for systemic therapeutic applications. One possible approach to minimize systemic toxicity is to generate a latent wortmannin pro-drug that will be selectively activated in target tissues. To test this approach, a wortmannin derivative with a leucine linker attached to C20 has been synthesized and tested for inhibition of PI3K activity in prostate cancer cells. Analysis of PI3K pathway inhibition by Wormannin-Leu (Wn-L) and intact Wortmannin (Wn) showed that attachment of Leu at C-20 decreased potency of PI3K pathway inhibition 10-fold compared to intact wortmannin, yet exceeded the potency of a competitive PI3K inhibitor LY294002.
subject
wortmanin synthesis
PI3K inhibitor
prostate cancer
date
2020-03-09T18:18:26Z (accessioned)
2020-03-09T18:18:26Z (available)
7/20/18 (issued)
identifier
Synthesis and PI3 Kinase Inhibition Activity of a Wortmannin-Leucine Derivative. William Cantrell, Yue Huang, Antonio A. Menchaca, George Kulik, and Mark E. Welker, Molecules 2018, 23(7), 1791 (citation)
http://hdl.handle.net/10339/96049 (uri)
identifier
https://doi.org/10.3390/molecules23071791 (doi)
language
en (iso)
publisher
MDPI
rights
https://creativecommons.org/licenses/by/4.0/ (uri)
source
Molecules
type
Article

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