Characterization of the mechanism of action of the pan class i PI3K inhibitor NVP-BKM120 across a broad range of concentrations

Molecular Cancer Therapeutics

Volumn 11, Issue 8, 2012, Pages 1747-1757

  Brachmann, Saskia M ^a   Kleylein Sohn, Julia ^a   Gaulis, Swann ^a   Kauffmann, Audrey ^a   Blommers, Marcel J J ^a   Kazic Legueux, Malika ^a   Laborde, Laurent ^a   Hattenberger, Marc ^a   Stauffer, Fabian ^a   Vaxelaire, Juliane ^a   Romanet, Vincent ^a   Henry, Chrystèle ^a   Murakami, Masato ^a   Guthy, Daniel Alexander ^a   Sterker, Dario ^a   Bergling, Sebastian ^b   Wilson, Christopher ^b   Brümmendorf, Thomas ^a   Fritsch, Christine ^a   Garcia Echeverria, Carlos ^c   Sellers, William R ^d   Hofmann, Francesco ^a   Maira, Sauveur Michel ^a   more..

^a NOVARTIS PHARMA AG   (Switzerland)

^b Development and Molecular Pathways   (France)

^c SANOFI   (France)

^d NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 (1 CYANO 1 METHYLETHYL) 3 METHYL 8 (3 QUINOLINYL)IMIDAZO[4,5 C]QUINOLIN 2(1H,3H) ONE; BUPARLISIB; NOCODAZOLE; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PICTRELISIB;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG EFFECT; DRUG MECHANISM; ENZYME INHIBITION; G2 PHASE CELL CYCLE CHECKPOINT; GENE EXPRESSION; HUMAN; HUMAN TISSUE; IN VITRO STUDY; IN VIVO STUDY; M PHASE CELL CYCLE CHECKPOINT; MICROTUBULE ASSEMBLY; MOUSE; NONHUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; TUMOR REGRESSION;

AMINOPYRIDINES; ANIMALS; CELL CYCLE CHECKPOINTS; CELL LINE, TUMOR; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; INDAZOLES; MICE; MITOSIS; MORPHOLINES; PHOSPHATIDYLINOSITOL 3-KINASES; PROTEIN MULTIMERIZATION; RATS; SULFONAMIDES; TUBULIN;

EID: 84864885418     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: 10.1158/1535-7163.MCT-11-1021     Document Type: Article

References (31)

1. Engelman JA, Luo J, Cantley LC. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet 2006;7:606-19. (Pubitemid 44100518)
2. Zhao L, Vogt PK. Class I PI3K in oncogenic cellular transformation. Oncogene 2008;27:5486-96.
3. Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, et al. High frequency of mutations of the PIK3CA gene in human cancers. Science 2004;304:554. (Pubitemid 38541907)
4. Sansal I, Sellers WR. The biology and clinical relevance of the PTEN tumor suppressor pathway. J Clin Oncol 2004;22:2954-63. (Pubitemid 41079915)
5. Hers I, Vincent EE, Tavaro JM. Akt signalling in health and disease. Cell Signal 2011;23:1515-27.
6. Urick ME, Rudd ML, Godwin AK, Sgroi D, Merino M, Bell DW. PIK3R1 (p85) is somatically mutated at high frequency in primary endometrial cancer. Cancer Res 2011;71:4061-7.
7. Sjödahl G, Lauss M, Gudjonsson S, Liedberg F, Halldén C, Chebil G, et al. A systematic study of gene mutations in urothelial carcinoma; inactivating mutations in TSC2 and PIK3R1. PLoS One 2011;6:e18583.
8. Alimandi M, Romano A, Curia MC, Muraro R, Fedi P, Aaronson SA, et al. Cooperative signaling of ErbB3 and ErbB2 in neoplastic transformation and human mammary carcinomas. Oncogene 1995;10:1813-21.
9. Shuttleworth SJ, Silva FA, Cecil AR, Tomassi CD, Hill TJ, Raynaud FI, et al. Progress in the preclinical discovery and clinical development of class I and dual class I/IV phosphoinositide 3-kinase (PI3K) inhibitors. Curr Med Chem 2011;18:2686-714.
10. Markman B, Atzori F, Perez-Garcia J, Tabernero J, Baselga J. Status of PI3K inhibition and biomarker development in cancer therapeutics. Ann Oncol 2010;21:683-91.
11. Maira SM, Pecchi S, Huang A, Burger M, Knapp M, Sterker D, et al. Identification and characterization of NVP-BKM120, an orally available pan class I PI3-Kinase inhibitor. Mol Cancer Ther 2012;11:317-28.
12. Gossert A, Henry C, Blommers M, Jahnke W, Fernandez C. Time efficient detection of protein-ligand interactions with the polarization optimized PO-WaterLOGSY NMR experiment. J Biomol NMR 2009;43:211-7.
13. Barretina J, Caponigro GV, Stransky N, Venkatesan K, Margolin AA, Kim S, et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 2012;483:603-7.
14. Brachmann SM, Hofmann I, Schnell C, Fritsch C, Wee S, Lane H, et al. 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;106:22299-304.
15. Maira SM, Stauffer F, Brueggen J, Furet P, Schnell C, Fritsch C, et al. 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;7:1851-63.
16. Jagani Z, Wiederschain D, Loo A, He D, Mosher R, Fordjour P, et al. The polycomb group protein Bmi-1 is essential for the growth of multiple myeloma cells. Cancer Res 2010;70:5528-38.
17. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: Aknowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A 2005;102:15545-50. (Pubitemid 41528093)
18. Szustakowski JD, Lee JH, Marrese CA, Kosinski PA, Nirmala NR, Kemp DM. Identification of novel pathway regulation during myogenic differentiation. Genomics 2006;87:129-38. (Pubitemid 43005109)
19. Newton M, Quintana F, den Boon J, Sengupta S, Ahlquist P. Random-set methods identify distinct aspects of the enrichment signal in gene-set analysis. Ann Appl Stat 2007;1:85-106.
20. R Development Core Team (2009). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN 3-900051-07-0, URLhttp://www.R-project.org/.
21. Folkes AJ, Ahmadi K, Alderton WK, Alix S, Baker SJ, Box G, et al. The identification of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl) -4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer. J Med Chem 2008;51:5522-32.
22. Raynaud FI, Eccles SA, Patel S, Alix S, Box G, Chuckowree I, et al. Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941. Mol Cancer Ther 2009;8:1725-38.
23. Carlomagno T, Blommers MJJ, Meiler J, Jahnke W, Schupp T, Petersen F, et al. The high-resolution solution structure of epothilone A bound to tubulin: an understanding of the structure to activity relationships for a powerful class of antitumor agents. Angew Chem Int Ed Engl 2003;42:2511-5. (Pubitemid 36753423)
24. Milas L, Hunter NR, Kurdoglu B, Mason KA, Meyn RE, Stephens LC, et al. Kinetics of mitotic arrest and apoptosis in murine mammary and ovarian tumors treated with taxol. Cancer Chemother Pharmacol 1995;35:297-303.
25. Weaver BA, Cleveland DW. Decoding the links between mitosis, cancer, and chemotherapy: the mitotic checkpoint, adaptation, and cell death. Cancer Cell 2005;8:7-12. (Pubitemid 40991810)
26. Nogales E, Wolf S, Khan IA, Luduena R, Downing K. Structure of tubulin at 6.5 A and location of the taxol-binding site. Nature 1995;375:424-7.
27. Gigant B, Wang C, Ravelli RBG, Roussi F, Steinmetz MO, Curmi PA, et al. Structural basis for the regulation of tubulin by vinblastine. Nature 2005;435:519-22. (Pubitemid 40734250)
28. Ravelli RBG, Gigant B, Curmi PA, Jourdain I, Lachkar S, Sobel A, et al. Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain. Nature 2004;428:198-202. (Pubitemid 38374318)
29. Nguyen TL, McGrath C, Hermone AR, Burnett JC, Zaharevitz DW, Day BW, et al. A common pharmacophore for a diverse set of colchicine site inhibitors using a structure-based approach. J Med Chem 2005;48:6107-16. (Pubitemid 41324618)
30. Chen J, Liu T, Dong X, Hu Y. Recent development and SAR analysis of colchicine binding site inhibitors. Mini Rev Med Chem 2009;9:1174-90.
31. Baselga J, De Jonge MJ, Rodon J, Burris HA, Birle DC, De Buck SS, et al. A first-in-human phase I study of BKM120, an oral pan-class I PI3K inhibitor, in patients with advanced solid tumors. J Clin Oncol 28:15s, 2010 (suppl; abstr 3003).