17β-hydroxy Wortmannin

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).¹ 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).² The 17-hydroxyl group has been used to further modify this compound, e.g., by pegylation and conjugation with rapamycin.^3,4

WARNING This product is not for human or veterinary use.

1. Thelen, M., Wymann, M.P., and Langen, H. Wortmannin binds specifically to 1-phosphatidylinositol 3-kinase while inhibiting guanine nucleotide-binding protein-coupled receptor signaling in neutrophil leukocytes. Proc. Natl. Acad. Sci. USA 91(11), 4960-4964 (1994).

2. Zask, A., Kaplan, J., Toral-Barza, L., 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. 51(5), 1319-1323 (2008).

3. Zhu, T., Gu, J., Yu, K., et al. Pegylated wortmannin and 17-hydroxywortmannin conjugates as phosphoinositide 3-kinase inhibitors active in human tumor xenograft models. J. Med. Chem. 49(4), 1373-1378 (2006).

4. Ayral-Kaloustian, S., Gu, J., Lucas, J., et al. Hybrid inhibitors of phosphatidylinositol 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR): Design, synthesis, and superior antitumor activity of novel wortmannin-rapamycin conjugates. J. Med. Chem. 53(1), 452-459 (2010).