PX-866

• CAT Number: R024647
• CAS Number: 502632-66-8
• Molecular Formula: C₂₉H₃₅NO₈
• Molecular Weight: 525.59
• Purity: ≥95%
• Target: PI3K
• Solubility: Soluble in DMSO
• Storage: Store at -20°C
• InChI: InChI=1S/C29H35NO8/c1-7-11-30(12-8-2)14-17-23-26(34)25(33)22-18-9-10-20(32)28(18,4)13-19(37-16(3)31)24(22)29(23,5)21(15-36-6)38-27(17)35/h7-8,14,18-19,21,34H,1-2,9-13,15H2,3-6H3/b17-14+/t18-,19+,21+,28-,29-/m0/s1
• InChIKey: QIUASFSNWYMDFS-NILGECQDSA-N
• SMILES: CC(=O)OC1CC2(C(CCC2=O)C3=C1C4(C(OC(=O)C(=CN(CC=C)CC=C)C4=C(C3=O)O)COC)C)C

Sonolisib, also known as PX-866, is a small-molecule wortmannin analogue inhibitor of the alpha, gamma, and delta isoforms of phosphoinositide 3-kinase (PI3K) with potential antineoplastic activity. PI3K inhibitor PX-866 inhibits the production of the secondary messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3) and activation of the PI3K/Akt signaling pathway, which may result in inhibition of tumor cell growth and survival in susceptible tumor cell populations. Activation of the PI3K/Akt signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K/Akt signaling may contribute to tumor resistance to a variety of antineoplastic agents.

Reference

1:Erratum to /Down-regulation of hTERT and Cyclin D1 transcription via PI3K/Akt and TGF-β pathways in MCF-7 cancer cells with PX-866 and Raloxifene/ [Exp. Cell Res. 344 (2016) 95-102]. Peek GW, Tollefsbol TO.Exp Cell Res. 2016 Jul 15;345(2):255. doi: 10.1016/j.yexcr.2016.05.021. Epub 2016 Jun 2. No abstract available. PMID: 27265745 2:A Randomized, Phase II Trial of Cetuximab With or Without PX-866, an Irreversible Oral Phosphatidylinositol 3-Kinase Inhibitor, in Patients With Metastatic Colorectal Carcinoma. Bowles DW, Kochenderfer M, Cohn A, Sideris L, Nguyen N, Cline-Burkhardt V, Schnadig I, Choi M, Nabell L, Chaudhry A, Ruxer R, Ucar A, Hausman D, Walker L, Spira A, Jimeno A.Clin Colorectal Cancer. 2016 Dec;15(4):337-344.e2. doi: 10.1016/j.clcc.2016.03.004. Epub 2016 Mar 31. PMID: 27118441 3:Down-regulation of hTERT and Cyclin D1 transcription via PI3K/Akt and TGF-β pathways in MCF-7 Cancer cells with PX-866 and Raloxifene. Peek GW, Tollefsbol TO.Exp Cell Res. 2016 May 15;344(1):95-102. doi: 10.1016/j.yexcr.2016.03.022. Epub 2016 Mar 23. PMID: 27017931 Free PMC Article4:Combinatorial PX-866 and Raloxifene Decrease Rb Phosphorylation, Cyclin E2 Transcription, and Proliferation of MCF-7 Breast Cancer Cells. Peek GW, Tollefsbol TO.J Cell Biochem. 2016 Jul;117(7):1688-96. doi: 10.1002/jcb.25462. Epub 2015 Dec 28. PMID: 26660119 Free PMC Article5:Phase II study of PX-866 in recurrent glioblastoma. Pitz MW, Eisenhauer EA, MacNeil MV, Thiessen B, Easaw JC, Macdonald DR, Eisenstat DD, Kakumanu AS, Salim M, Chalchal H, Squire J, Tsao MS, Kamel-Reid S, Banerji S, Tu D, Powers J, Hausman DF, Mason WP.Neuro Oncol. 2015 Sep;17(9):1270-4. doi: 10.1093/neuonc/nou365. Epub 2015 Jan 20. PMID: 25605819 Free PMC Article6:A randomized, phase 2 trial of docetaxel with or without PX-866, an irreversible oral phosphatidylinositol 3-kinase inhibitor, in patients with relapsed or metastatic head and neck squamous cell cancer. Jimeno A, Bauman JE, Weissman C, Adkins D, Schnadig I, Beauregard P, Bowles DW, Spira A, Levy B, Seetharamu N, Hausman D, Walker L, Rudin CM, Shirai K.Oral Oncol. 2015 Apr;51(4):383-8. doi: 10.1016/j.oraloncology.2014.12.013. Epub 2015 Jan 13. PMID: 25593016 Free PMC Article7:A randomized, phase II trial of cetuximab with or without PX-866, an irreversible oral phosphatidylinositol 3-kinase inhibitor, in patients with relapsed or metastatic head and neck squamous cell cancer. Jimeno A, Shirai K, Choi M, Laskin J, Kochenderfer M, Spira A, Cline-Burkhardt V, Winquist E, Hausman D, Walker L, Cohen RB.Ann Oncol. 2015 Mar;26(3):556-61. doi: 10.1093/annonc/mdu574. Epub 2014 Dec 18. PMID: 25524478 8:A randomized, phase 2 trial of Docetaxel with or without PX-866, an irreversible oral phosphatidylinositol 3-kinase inhibitor, in patients with relapsed or metastatic non-small-cell lung cancer. Levy B, Spira A, Becker D, Evans T, Schnadig I, Camidge DR, Bauman JE, Hausman D, Walker L, Nemunaitis J, Rudin CM, Halmos B, Bowles DW.J Thorac Oncol. 2014 Jul;9(7):1031-5. doi: 10.1097/JTO.0000000000000183. PMID: 24926548 Free Article9:A multicenter phase 1 study of PX-866 and cetuximab in patients with metastatic colorectal carcinoma or recurrent/metastatic squamous cell carcinoma of the head and neck. Bowles DW, Senzer N, Hausman D, Peterson S, Vo A, Walker L, Cohen RB, Jimeno A.Invest New Drugs. 2014 Dec;32(6):1197-203. doi: 10.1007/s10637-014-0124-3. Epub 2014 Jun 12. PMID: 24916771 10:A multicenter phase 1 study of PX-866 in combination with docetaxel in patients with advanced solid tumours. Bowles DW, Ma WW, Senzer N, Brahmer JR, Adjei AA, Davies M, Lazar AJ, Vo A, Peterson S, Walker L, Hausman D, Rudin CM, Jimeno A.Br J Cancer. 2013 Sep 3;109(5):1085-92. doi: 10.1038/bjc.2013.474. Epub 2013 Aug 13. PMID: 23942080 Free PMC Article