PX 866

PX 866 is a ring-opened analog of wortmannin (Item No. 10010591) that potently and irreversibly inhibits PI3K (IC₅₀ = 0.1-88 nM).^1,2 It less potently blocks the activity of mammalian target of rapamycin (mTOR, IC₅₀ = 3.1 µM).² PX 866 exhibits single agent in vivo anti-tumor activity and increases the anti-tumor effects of cisplatin and radiation treatment.^1,3 In cancer cells grown in three-dimensional cultures, PX 866 reduces cell growth and motility without causing cytotoxicity.⁴ Consistent with having cytostatic effects, PX 866 dosing is associated with prolonged stable disease in cancer patients.⁵

WARNING This product is not for human or veterinary use.

1. Ihle, N.T., Williams, R., Chow, S., et al. Molecular pharmacology and antitumor activity of PX-866, a novel inhibitor of phosphoinositide-3-kinase signaling. Mol. Cancer Ther. 3(7), 763-772 (2004).

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. Ihle, N.T., Paine-Murrieta, G., Berggren, M.I., et al. The phosphatidylinositol-3-kinase inhibitor PX-866 overcomes resistance to the epidermal growth factor receptor inhibitor gefitinib in A-549 human non-small cell lung cancer xenografts. Mol. Cancer Ther. 4(9), 1349-1357 (2005).

4. Howes, A.L., Chiang, G.G., Lang, E.S., et al. The phosphatidylinositol 3-kinase inhibitor, PX-866, is a potent inhibitor of cancer cell motility and growth in three-dimensional cultures. Mol. Cancer Ther. 6(9), 2505-2514 (2007).

5. Hong, D.S., Bowles, D.W., Falchook, G.S., et al. A Multicenter phase I trial of PX-866, an oral irreversible phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors. Clin. Cancer Res. 18(15), 4173-4182 (2012).