Item Details

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

contributor

Cantrell, W. (author)

Huang, Y. (author)

Menchaca, A. (author)

Kulik, G. (author)

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)

https://doi.org/10.3390/molecules23071791 (doi)

http://hdl.handle.net/10339/96049 (uri)

language

en (iso)

publisher

MDPI

rights

https://creativecommons.org/licenses/by/4.0/ (uri)

source

Molecules

title

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

type

Article