17β-hydroxy Wortmannin

Description

17β-hydroxy Wortmannin is an analog of wortmannin. It irreversibly binds phosphoinositide 3-kinase (PI3K) and potently blocks fMLP-stimulated respiratory burst in neutrophils (IC₅₀ = 5 nM). 17β-hydroxy Wortmannin inhibits recombinant PI3K and mTOR (IC₅₀ = 2.7 and 193 nM, respectively) and prevents the growth of LNCap prostate cancer cells (IC₅₀ = 1.46 μM). The 17-hydroxyl group has been used to further modify this compound, e.g., by pegylation and conjugation with rapamycin.

Uses

17β-Hydroxywortmannin (Wortmannin-17β-ol) is an orally active inhibitor for phosphatidylinositol-3-kinase (PI-3-kinase) with an IC50 of 0.5 nM, suppresses the osteoclast resorption with an IC50 of 10 nM[1]. 17β-Hydroxywortmannin exhibits antitumor activity[2].

in vivo

IC 50

PI3K: 0.5 nM (IC₅₀)

References

[1] Hall TJ, et al., Wortmannin, a potent inhibitor of phosphatidylinositol 3-kinase, inhibits osteoclastic bone resorption in vitro. Calcif Tissue Int. 1995 Apr;56(4):336-8. DOI:10.1007/BF00318056
[2] Zask A, et al., Synthesis and structure-activity relationships of ring-opened 17-hydroxywortmannins: potent phosphoinositide 3-kinase inhibitors with improved properties and anticancer efficacy. J Med Chem. 2008 Mar 13;51(5):1319-23. DOI:10.1021/jm7012858