Selective inhibition of phosphoinositide 3-kinase p110 α preserves lymphocyte function

Journal of Biological Chemistry

Volumn 288, Issue 8, 2013, Pages 5718-5731

  So, Lomon ^a   Yea, Sung Su ^a,b   Oak, Jean S ^a   Lu, Mengrou ^a   Manmadhan, Arun ^a   Ke, Qiao Han ^a   Janes, Matthew R ^c,d   Kessler, Linda V ^c,d   Kucharski, Jeff M ^c,d   Li, Lian Sheng ^c,d   Martin, Michael B ^c,d   Ren, Pingda ^c   Jessen, Katti A ^c,d   Liu, Yi ^c   Rommel, Christian ^c   Fruman, David A ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b Inje University   (South Korea)

^c Intellikine Inc   (United States)

^d Takeda San Diego Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CANCER THERAPY; DRUG TARGETS; IN-VITRO; ISOFORMS; PHOSPHOINOSITIDE 3-KINASE; SELECTIVE INHIBITION;

ONCOLOGY;

LYMPHOCYTES;

2 (2 DIFLUOROMETHYLBENZIMIDAZOL 1 YL) 4,6 DIMORPHOLINO 1,3,5 TRIAZINE; 2 (6 AMINO 9 PURINYLMETHYL) 5 METHYL 3 (2 METHYLPHENYL) 3H QUINAZOLIN 4 ONE; 9 (1 ANILINOETHYL) 7 METHYL 2 MORPHOLINOPYRIDO[1,2 A]PYRIMIDIN 4 ONE; C8 7114; MLN 1117; PHENMETRAZINE; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PICTILISIB; PROTEIN KINASE B; PROTEIN P110ALPHA; PROTEIN P110ALPHA INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CD4+ T LYMPHOCYTE; CONTROLLED STUDY; DRUG DESIGN; DRUG MECHANISM; DRUG SELECTIVITY; DRUG TARGETING; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; LYMPHOCYTE FUNCTION; LYMPHOCYTE PRESERVATION; LYMPHOCYTE PROLIFERATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN CROSS LINKING; QUANTITATIVE ANALYSIS;

ANIMALS; CALCIUM; CELL LINE, TUMOR; CELL PROLIFERATION; CLASS IA PHOSPHATIDYLINOSITOL 3-KINASE; DRUG DESIGN; ENZYME INHIBITORS; ENZYME-LINKED IMMUNOSORBENT ASSAY; GENE EXPRESSION REGULATION, ENZYMOLOGIC; HUMANS; IMMUNOSUPPRESSIVE AGENTS; LYMPHOCYTES; MICE; MICE, INBRED BALB C; NEOPLASMS; PROTEIN ISOFORMS; SIGNAL TRANSDUCTION; SPLEEN; T-LYMPHOCYTES;

EID: 84874301974     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M112.379446     Document Type: Article

References (43)

1. Vanhaesebroeck, B., Guillermet-Guibert, J., Graupera, M., and Bilanges, B. (2010) The emerging mechanisms of isoform-specific PI3K signalling. Nat. Rev. Mol. Cell Biol. 11, 329-341
2. Agarwal, R., Carey, M., Hennessy, B., and Mills, G. B. (2010) PI3K pathway-directed therapeutic strategies in cancer. Curr. Opin. Investig. Drugs 11, 615-628
3. + inhibitors in cancer. Rationale and serendipity merge in the clinic. Cancer Discov. 1, 562-572
4. Hanahan, D., and Weinberg, R. A. (2011) Hallmarks of cancer: the next generation. Cell 144, 646-674
5. Wong, K. K., Engelman, J. A., and Cantley, L. C. (2010) Targeting the PI3K signaling pathway in cancer. Curr. Opin. Gen. Dev. 20, 87-90
6. Samuels, Y., Wang, Z., Bardelli, A., Silliman, N., Ptak, J., Szabo, S., Yan, H., Gazdar, A., Powell, S. M., Riggins, G. J., Willson, J. K., Markowitz, S., Kinzler, K. W., Vogelstein, B., and Velculescu, V. E. (2004) High frequency of mutations of the PIK3CA gene in human cancers. Science 304, 554
7. Engelman, J. A., Chen, L., Tan, X., Crosby, K., Guimaraes, A. R., Upadhyay, R., Maira, M., McNamara, K., Perera, S. A., Song, Y., Chirieac, L. R., Kaur, R., Lightbown, A., Simendinger, J., Li, T., Padera, R. F., García-Echeverría, C., Weissleder, R., Mahmood, U., Cantley, L. C., and Wong, K. K. (2008) Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat. Med. 14, 1351-1356
8. Liu, P., Cheng, H., Santiago, S., Raeder, M., Zhang, F., Isabella, A., Yang, J., Semaan, D. J., Chen, C., Fox, E. A., Gray, N. S., Monahan, J., Schlegel, R., Beroukhim, R., Mills, G. B., and Zhao, J. J. (2011) Oncogenic PIK3CAdriven mammary tumors frequently recur via PI3K pathway-dependent and PI3K pathway-independent mechanisms. Nat. Med. 17, 1116-1120
9. Jamieson, S., Flanagan, J. U., Kolekar, S., Buchanan, C., Kendall, J. D., Lee, W. J., Rewcastle, G. W., Denny, W. A., Singh, R., Dickson, J., Baguley, B. C., and Shepherd, P. R. (2011) A drug targeting only p110-can block phosphoinositide 3-kinase signalling and tumour growth in certain cell types. Biochem. J. 438, 53-62
10. O'Brien, C., Wallin, J. J., Sampath, D., GuhaThakurta, D., Savage, H., Punnoose, E. A., Guan, J., Berry, L., Prior, W. W., Amler, L. C., Belvin, M., Friedman, L. S., and Lackner, M. R. (2010) Predictive biomarkers of sensitivity to the phosphatidylinositol 3-kinase inhibitor GDC-0941 in breast cancer preclinical models. Clin. Cancer Res. 16, 3670-3683
11. Edgar, K. A., Wallin, J. J., Berry, M., Lee, L. B., Prior, W. W., Sampath, D., Friedman, L. S., and Belvin, M. (2010) Isoform-specific phosphoinositide 3-kinase inhibitors exert distinct effects in solid tumors. Cancer Res. 70, 1164-1172
12. Jia, S., Liu, Z., Zhang, S., Liu, P., Zhang, L., Lee, S. H., Zhang, J., Signoretti, S., Loda, M., Roberts, T. M., and Zhao, J. J. (2008) Essential roles of PI(3)Kp110-in cell growth, metabolism and tumorigenesis. Nature 454, 776-779
13. Deleted in proof
14. Rakhra, K., Bachireddy, P., Zabuawala, T., Zeiser, R., Xu, L., Kopelman, A., Fan, A. C., Yang, Q., Braunstein, L., Crosby, E., Ryeom, S., and Felsher, D. W. (2010) CD4-T cells contribute to the remodeling of the microenvironment required for sustained tumor regression upon oncogene inactivation. Cancer Cell 18, 485-498
15. Vanneman, M., and Dranoff, G. (2012) Combining immunotherapy and targeted therapies in cancer treatment. Nat. Rev. Cancer 12, 237-251
16. Okkenhaug, K., and Fruman, D. A. (2010) PI3Ks in lymphocyte signaling and development. Curr. Top. Microbiol. Immunol. 346, 57-85
17. Bi, L., Okabe, I., Bernard, D. J., Wynshaw-Boris, A., and Nussbaum, R. L. (1999) Proliferative defect and embryonic lethality in mice homozygous for a deletion in the p110-subunit of phosphoinositide 3-kinase. J. Biol. Chem. 274, 10963-10968
18. Foukas, L. C., Claret, M., Pearce, W., Okkenhaug, K., Meek, S., Peskett, E., Sancho, S., Smith, A. J., Withers, D. J., and Vanhaesebroeck, B. (2006) Critical role for the p110-phosphoinositide-3-OH kinase in growth and metabolic regulation. Nature 441, 366-370
19. Graupera, M., Guillermet-Guibert, J., Foukas, L. C., Phng, L. K., Cain, R. J., Salpekar, A., Pearce, W., Meek, S., Millan, J., Cutillas, P. R., Smith, A. J., Ridley, A. J., Ruhrberg, C., Gerhardt, H., and Vanhaesebroeck, B. (2008) Angiogenesis selectively requires the p110-isoform of PI3K to control endothelial cell migration. Nature 453, 662-666
20. Ramadani, F., Bolland, D. J., Garcon, F., Emery, J. L., Vanhaesebroeck, B., Corcoran, A. E., and Okkenhaug, K. (2010) The PI3K isoforms p110-and p110-are essential for pre-B cell receptor signaling and B cell development. Sci. Signal 3, ra60
21. Janes, M. R., Limon, J. J., So, L., Chen, J., Lim, R. J., Chavez, M. A., Vu, C., Lilly, M. B., Mallya, S., Ong, S. T., Konopleva, M., Martin, M. B., Ren, P., Liu, Y., Rommel, C., and Fruman, D. A. (2010) Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor. Nat. Med. 16, 205-213
22. Donahue, A. C., and Fruman, D. A. (2007) Distinct signaling mechanisms activate the target of rapamycin in response to different B-cell stimuli. Eur. J. Immunol. 37, 2923-2936
23. Sun, M., Hillmann, P., Hofmann, B. T., Hart, J. R., and Vogt, P. K. (2010) Cancer-derived mutations in the regulatory subunit p85-of phosphoinositide 3-kinase function through the catalytic subunit p110-. Proc. Natl. Acad. Sci. U.S.A. 107, 15547-15552
24. Jessen, K., Kessler, L., Kucharski, J., Guo, X., Staunton, J., Janes, M. R., Elia, M., Banerjee, U., Lan, L., Wang, S., Stewart, J., Luzader, A., Darjania, L., Li, L., Chan, K., Martin, M., Ren, P., Rommel, C., and Liu, Y. (2011) A potent and selective PI3K inhibitor, INK1117, targets human cancers harboring oncogenic PIK3CA mutations. Mol. Cancer Ther. 10, Abstr. A171
25. Chaussade, C., Rewcastle, G. W., Kendall, J. D., Denny, W. A., Cho, K., Grønning, L. M., Chong, M. L., Anagnostou, S. H., Jackson, S. P., Daniele, N., and Shepherd, P. R. (2007) Evidence for functional redundancy of class IA PI3K isoforms in insulin signalling. Biochem. J. 404, 449-458
26. Jackson, S. P., Schoenwaelder, S. M., Goncalves, I., Nesbitt, W. S., Yap, C. L., Wright, C. E., Kenche, V., Anderson, K. E., Dopheide, S. M., Yuan, Y., Sturgeon, S. A., Prabaharan, H., Thompson, P. E., Smith, G. D., Shepherd, P. R., Daniele, N., Kulkarni, S., Abbott, B., Saylik, D., Jones, C., Lu, L., Giuliano, S., Hughan, S. C., Angus, J. A., Robertson, A. D., and Salem, H. H. (2005) PI 3-kinase p110-. A new target for antithrombotic therapy. Nat. Med. 11, 507-514
27. Bilancio, A., Okkenhaug, K., Camps, M., Emery, J. L., Ruckle, T., Rommel, C., and Vanhaesebroeck, B. (2006) Key role of the p110-isoform of PI3K in B-cell antigen and IL-4 receptor signaling. Comparative analysis of genetic and pharmacologic interference with p110-function in B cells. Blood 107, 642-650
28. Durand, C. A., Hartvigsen, K., Fogelstrand, L., Kim, S., Iritani, S., Vanhaesebroeck, B., Witztum, J. L., Puri, K. D., and Gold, M. R. (2009) Phosphoinositide 3-kinase p110-regulates natural antibody production, marginal zone and B-1 B cell function, and autoantibody responses. J. Immunol. 183, 5673-5684
29. Soond, D. R., Bjørgo, E., Moltu, K., Dale, V. Q., Patton, D. T., Torgersen, K. M., Galleway, F., Twomey, B., Clark, J., Gaston, J. S., Taskén, K., Bunyard, P., and Okkenhaug, K. (2010) PI3K p110-regulates T-cell cytokine production during primary and secondary immune responses in mice and humans. Blood 115, 2203-2213
30. Folkes, A. J., Ahmadi, K., Alderton, W. K., Alix, S., Baker, S. J., Box, G., Chuckowree, I. S., Clarke, P. A., Depledge, P., Eccles, S. A., Friedman, L. S., Hayes, A., Hancox, T. C., Kugendradas, A., Lensun, L., Moore, P., Olivero, A. G., Pang, J., Patel, S., Pergl-Wilson, G. H., Raynaud, F. I., Robson, A., Saghir, N., Salphati, L., Sohal, S., Ultsch, M. H., Valenti, M., Wallweber, H. J., Wan, N. C., Wiesmann, C., Workman, P., Zhyvoloup, A., Zvelebil, M. J., and Shuttleworth, S. J. (2008) The identification of 2-(1H-indazol-4-yl)-6-(4- methanesulfonyl-piperazin-1-yl-methyl)-4-morpholine-4-ylthieno[ 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. 51, 5522-5532
31. Raynaud, F. I., Eccles, S. A., Patel, S., Alix, S., Box, G., Chuckowree, I., Folkes, A., Gowan, S., De Haven Brandon, A., Di Stefano, F., Hayes, A., Henley, A. T., Lensun, L., Pergl-Wilson, G., Robson, A., Saghir, N., Zhyvoloup, A., McDonald, E., Sheldrake, P., Shuttleworth, S., Valenti, M., Wan, N. C., Clarke, P. A., and Workman, P. (2009) 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. 8, 1725-1738
32. Kong, D., and Yamori, T. (2007) ZSTK474 is an ATP-competitive inhibitor of class I phosphatidylinositol 3-kinase isoforms. Cancer Sci. 98, 1638-1642
33. Rewcastle, G. W., Gamage, S. A., Flanagan, J. U., Frederick, R., Denny, W. A., Baguley, B. C., Kestell, P., Singh, R., Kendall, J. D., Marshall, E. S., Lill, C. L., Lee, W. J., Kolekar, S., Buchanan, C. M., Jamieson, S. M., and Shepherd, P. R. (2011) Synthesis and biological evaluation of novel analogues of the pan class I phosphatidylinositol 3-kinase (PI3K) inhibitor 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1Hbenzimidazole (ZSTK474). J. Med. Chem. 54, 7105-7126
34. Wee, S., Wiederschain, D., Maira, S. M., Loo, A., Miller, C., deBeaumont, R., Stegmeier, F., Yao, Y. M., and Lengauer, C. (2008) PTEN-deficient cancers depend on PIK3CB. Proc. Natl. Acad. Sci. U.S.A. 105, 13057-13062
35. Okkenhaug, K., Ali, K., and Vanhaesebroeck, B. (2007) Antigen receptor signalling. A distinctive role for the p110-isoform of PI3K. Trends Immunol. 28, 80-87
36. Fruman, D. A., Satterthwaite, A. B., and Witte, O. N. (2000) Xid-like phenotypes. A B cell signalosome takes shape. Immunity 13, 1-3
37. Okkenhaug, K., Bilancio, A., Farjot, G., Priddle, H., Sancho, S., Peskett, E., Pearce, W., Meek, S. E., Salpekar, A., Waterfield, M. D., Smith, A. J., and Vanhaesebroeck, B. (2002) Impaired B and T cell antigen receptor signaling in p110-PI 3-kinase mutant mice. Science 297, 1031-1034
38. Okkenhaug, K., Patton, D. T., Bilancio, A., Garçon, F., Rowan, W. C., and Vanhaesebroeck, B. (2006) The p110-isoform of phosphoinositide 3-ki-nase controls clonal expansion and differentiation of Th cells. J. Immunol. 177, 5122-5128
39. Zhang, T. T., Okkenhaug, K., Nashed, B. F., Puri, K. D., Knight, Z. A., Shokat, K. M., Vanhaesebroeck, B., and Marshall, A. J. (2008) Genetic or pharmaceutical blockade of p110-phosphoinositide 3-kinase enhances IgE production. J. Allergy Clin. Immunol. 122, 811-819.e2
40. So, L., and Fruman, D. A. (2012) PI3K signalling in B-and T-lymphocytes. New developments and therapeutic advances. Biochem. J. 442, 465-481
41. Rolf, J., Bell, S. E., Kovesdi, D., Janas, M. L., Soond, D. R., Webb, L. M., Santinelli, S., Saunders, T., Hebeis, B., Killeen, N., Okkenhaug, K., and Turner, M. (2010) Phosphoinositide 3-kinase activity in T cells regulates the magnitude of the germinal center reaction. J. Immunol. 185, 4042-4052
42. Workman, P., Clarke, P. A., Raynaud, F. I., and van Montfort, R. L. (2010) Drugging the PI3 kinome. From chemical tools to drugs in the clinic. Cancer Res. 70, 2146-2157
43. Marshall, N. A., Galvin, K. C., Corcoran, A. M., Boon, L., Higgs, R., and Mills, K. H. (2012) Immunotherapy with PI3K inhibitor and Toll-like receptor agonist induces IFN-IL-17-polyfunctional T cells that mediate rejection of murine tumors. Cancer Res. 72, 581-591