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MedKoo product information:

BEZ235

Description of BEZ235: BEZ235 is an orally bioavailable phosphatidylinositol 3-kinase (PI3K) inhibitor with potential antineoplastic activity. PI3K inhibitor BEZ235 specifically inhibits PIK3 in the PI3K/AKT kinase (or protein kinase B) signaling pathway, which may trigger the translocation of cytosolic Bax to the mitochondrial outer membrane, increasing mitochondrial membrane permeability; apoptotic cell death may ensue. Bax is a member of the proapoptotic Bcl2 family of proteins. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Current developer:   Novartis.

BEZ235 is a dual phosphatidylinositol 3-kinase (PI(3)K)/mammalian target of rapamycin (mTOR) inhibitor that is orally available and that has been shown to be effective in several malignancies in vitro. Recently, BEZ235 entered clinical trials for solid tumors.

1: Hernlund E, Olofsson MH, Fayad W, Fryknäs M, Lesiak-Mieczkowska K, Zhang X, Brnjic S, Schmidt V, D'Arcy P, Sjöblom T, Milito AD, Larsson R, Linder S. The phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 is effective in inhibiting regrowth of tumour cells after cytotoxic therapy. Eur J Cancer. 2011 Dec 7. [Epub ahead of print] PubMed PMID: 22154651.

2: Maira SM. PI3K inhibitors for cancer treatment: five years of preclinical and clinical research after BEZ235. Mol Cancer Ther. 2011 Nov;10(11):2016. PubMed PMID: 22072802.

3: Awasthi N, Yen PL, Schwarz MA, Schwarz RE. The efficacy of a novel, dual PI3K/mTOR inhibitor NVP-BEZ235 to enhance chemotherapy and antiangiogenic response in pancreatic cancer. J Cell Biochem. 2011 Oct 20. doi: 10.1002/jcb.23405. [Epub ahead of print] PubMed PMID: 22020918.

4: Roper J, Richardson MP, Wang WV, Richard LG, Chen W, Coffee EM, Sinnamon MJ, Lee L, Chen PC, Bronson RT, Martin ES, Hung KE. The dual PI3K/mTOR inhibitor NVP-BEZ235 induces tumor regression in a genetically engineered mouse model of PIK3CA wild-type colorectal cancer. PLoS One. 2011;6(9):e25132. Epub 2011 Sep 26. PubMed PMID: 21966435; PubMed Central PMCID: PMC3180374.

5: Roulin D, Waselle L, Dormond-Meuwly A, Dufour M, Demartines N, Dormond O. Targeting renal cell carcinoma with NVP-BEZ235, a dual PI3K/mTOR inhibitor, in combination with sorafenib. Mol Cancer. 2011 Jul 26;10:90. PubMed PMID: 21791089; PubMed Central PMCID: PMC3160413.

6: Masuda M, Shimomura M, Kobayashi K, Kojima S, Nakatsura T. Growth inhibition by NVP-BEZ235, a dual PI3K/mTOR inhibitor, in hepatocellular carcinoma cell lines. Oncol Rep. 2011 Nov;26(5):1273-9. doi: 10.3892/or.2011.1370. Epub 2011 Jul 1. PubMed PMID: 21725613.

7: Fuereder T, Wanek T, Pflegerl P, Jaeger-Lansky A, Hoeflmayer D, Strommer S, Kuntner C, Wrba F, Werzowa J, Hejna M, Müller M, Langer O, Wacheck V. Gastric cancer growth control by BEZ235 in vivo does not correlate with PI3K/mTOR target inhibition but with [18F]FLT uptake. Clin Cancer Res. 2011 Aug 15;17(16):5322-32. doi: 10.1158/1078-0432.CCR-10-1659. Epub 2011 Jun 28. PubMed PMID: 21712451.

8: Xu CX, Li Y, Yue P, Owonikoko TK, Ramalingam SS, Khuri FR, Sun SY. The combination of RAD001 and NVP-BEZ235 exerts synergistic anticancer activity against non-small cell lung cancer in vitro and in vivo. PLoS One. 2011;6(6):e20899. Epub 2011 Jun 14. PubMed PMID: 21695126; PubMed Central PMCID: PMC3114848.

9: Herrera VA, Zeindl-Eberhart E, Jung A, Huber RM, Bergner A. The dual PI3K/mTOR inhibitor BEZ235 is effective in lung cancer cell lines. Anticancer Res. 2011 Mar;31(3):849-54. PubMed PMID: 21498705.

10: Leung E, Kim JE, Rewcastle GW, Finlay GJ, Baguley BC. Comparison of the effects of the PI3K/mTOR inhibitors NVP-BEZ235 and GSK2126458 on tamoxifen-resistant breast cancer cells. Cancer Biol Ther. 2011 Jun 1;11(11):938-46. Epub 2011 Jun 1. PubMed PMID: 21464613; PubMed Central PMCID: PMC3127046.

11: Santiskulvong C, Konecny GE, Fekete M, Chen KY, Karam A, Mulholland D, Eng C, Wu H, Song M, Dorigo O. Dual targeting of phosphoinositide 3-kinase and mammalian target of rapamycin using NVP-BEZ235 as a novel therapeutic approach in human ovarian carcinoma. Clin Cancer Res. 2011 Apr 15;17(8):2373-84. Epub 2011 Mar 3. PubMed PMID: 21372221; PubMed Central PMCID: PMC3078990.

12: Brünner-Kubath C, Shabbir W, Saferding V, Wagner R, Singer CF, Valent P, Berger W, Marian B, Zielinski CC, Grusch M, Grunt TW. The PI3 kinase/mTOR blocker NVP-BEZ235 overrides resistance against irreversible ErbB inhibitors in breast cancer cells. Breast Cancer Res Treat. 2011 Sep;129(2):387-400. doi: 10.1007/s10549-010-1232-1. Epub 2010 Nov 3. PubMed PMID: 21046231.

13: Chapuis N, Tamburini J, Green AS, Vignon C, Bardet V, Neyret A, Pannetier M, Willems L, Park S, Macone A, Maira SM, Ifrah N, Dreyfus F, Herault O, Lacombe C, Mayeux P, Bouscary D. Dual inhibition of PI3K and mTORC1/2 signaling by NVP-BEZ235 as a new therapeutic strategy for acute myeloid leukemia. Clin Cancer Res. 2010 Nov 15;16(22):5424-35. Epub 2010 Sep 30. PubMed PMID: 20884625.

14: Chiarini F, Grimaldi C, Ricci F, Tazzari PL, Evangelisti C, Ognibene A, Battistelli M, Falcieri E, Melchionda F, Pession A, Pagliaro P, McCubrey JA, Martelli AM. Activity of the novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 against T-cell acute lymphoblastic leukemia. Cancer Res. 2010 Oct 15;70(20):8097-107. Epub 2010 Sep 28. PubMed PMID: 20876803.

15: Bhende PM, Park SI, Lim MS, Dittmer DP, Damania B. The dual PI3K/mTOR inhibitor, NVP-BEZ235, is efficacious against follicular lymphoma. Leukemia. 2010 Oct;24(10):1781-4. Epub 2010 Aug 12. PubMed PMID: 20703254; PubMed Central PMCID: PMC3027218.

16: Cho DC, Cohen MB, Panka DJ, Collins M, Ghebremichael M, Atkins MB, Signoretti S, Mier JW. The efficacy of the novel dual PI3-kinase/mTOR inhibitor NVP-BEZ235 compared with rapamycin in renal cell carcinoma. Clin Cancer Res. 2010 Jul 15;16(14):3628-38. Epub 2010 Jul 6. PubMed PMID: 20606035; PubMed Central PMCID: PMC2905505.

17: Martin SK, Fitter S, Bong LF, Drew JJ, Gronthos S, Shepherd PR, Zannettino AC. NVP-BEZ235, a dual pan class I PI3 kinase and mTOR inhibitor, promotes osteogenic differentiation in human mesenchymal stromal cells. J Bone Miner Res. 2010 Oct;25(10):2126-37. PubMed PMID: 20499346.

18: Manara MC, Nicoletti G, Zambelli D, Ventura S, Guerzoni C, Landuzzi L, Lollini PL, Maira SM, García-Echeverría C, Mercuri M, Picci P, Scotlandi K. NVP-BEZ235 as a new therapeutic option for sarcomas. Clin Cancer Res. 2010 Jan 15;16(2):530-40. Epub 2010 Jan 12. PubMed PMID: 20068094.

19: Brachmann SM, Hofmann I, Schnell C, Fritsch C, Wee S, Lane H, Wang S, Garcia-Echeverria C, Maira SM. Specific apoptosis induction by the dual PI3K/mTor inhibitor NVP-BEZ235 in HER2 amplified and PIK3CA mutant breast cancer cells. Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22299-304. Epub 2009 Dec 10. PubMed PMID: 20007781; PubMed Central PMCID: PMC2799764.

20: Liu TJ, Koul D, LaFortune T, Tiao N, Shen RJ, Maira SM, Garcia-Echevrria C, Yung WK. NVP-BEZ235, a novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor, elicits multifaceted antitumor activities in human gliomas. Mol Cancer Ther. 2009 Aug;8(8):2204-10. Epub 2009 Aug 11. PubMed PMID: 19671762; PubMed Central PMCID: PMC2752877.

21: McMillin DW, Ooi M, Delmore J, Negri J, Hayden P, Mitsiades N, Jakubikova J, Maira SM, Garcia-Echeverria C, Schlossman R, Munshi NC, Richardson PG, Anderson KC, Mitsiades CS. Antimyeloma activity of the orally bioavailable dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235. Cancer Res. 2009 Jul 15;69(14):5835-42. Epub 2009 Jul 7. PubMed PMID: 19584292.

22: Cao P, Maira SM, García-Echeverría C, Hedley DW. Activity of a novel, dual PI3-kinase/mTor inhibitor NVP-BEZ235 against primary human pancreatic cancers grown as orthotopic xenografts. Br J Cancer. 2009 Apr 21;100(8):1267-76. Epub 2009 Mar 24. PubMed PMID: 19319133; PubMed Central PMCID: PMC2676548.

23: Baumann P, Mandl-Weber S, Oduncu F, Schmidmaier R. The novel orally bioavailable inhibitor of phosphoinositol-3-kinase and mammalian target of rapamycin, NVP-BEZ235, inhibits growth and proliferation in multiple myeloma. Exp Cell Res. 2009 Feb 1;315(3):485-97. Epub 2008 Nov 27. PubMed PMID: 19071109.

24: Eichhorn PJ, Gili M, Scaltriti M, Serra V, Guzman M, Nijkamp W, Beijersbergen RL, Valero V, Seoane J, Bernards R, Baselga J. Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235. Cancer Res. 2008 Nov 15;68(22):9221-30. PubMed PMID: 19010894; PubMed Central PMCID: PMC2587064.

25: Serra V, Markman B, Scaltriti M, Eichhorn PJ, Valero V, Guzman M, Botero ML, Llonch E, Atzori F, Di Cosimo S, Maira M, Garcia-Echeverria C, Parra JL, Arribas J, Baselga J. NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutations. Cancer Res. 2008 Oct 1;68(19):8022-30. PubMed PMID: 18829560.

26: Schnell CR, Stauffer F, Allegrini PR, O'Reilly T, McSheehy PM, Dartois C, Stumm M, Cozens R, Littlewood-Evans A, García-Echeverría C, Maira SM. Effects of the dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 on the tumor vasculature: implications for clinical imaging. Cancer Res. 2008 Aug 15;68(16):6598-607. PubMed PMID: 18701483.

27: Maira SM, Stauffer F, Brueggen J, Furet P, Schnell C, Fritsch C, Brachmann S, Chène P, De Pover A, Schoemaker K, Fabbro D, Gabriel D, Simonen M, Murphy L, Finan P, Sellers W, García-Echeverría C. Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity. Mol Cancer Ther. 2008 Jul;7(7):1851-63. Epub 2008 Jul 7. PubMed PMID: 18606717.