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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
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 USA914960-4964(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 Chem511319-1323(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 Chem491373-1378(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 Chem53(1)452-459(2010).
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 Chem491373-1378(2006).
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 USA914960-4964(1994).
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 Chem53(1)452-459(2010).
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 Chem511319-1323(2008).