A novel imidazopyridine analogue as a phosphatidylinositol 3-kinase inhibitor against human breast cancer

Cancer Letters

Volumn 318, Issue 1, 2012, Pages 68-75

  Lee, Hyunseung ^a   Li, Guang Yong ^a   Jeong, Yujeong ^b   Jung, Kyung Hee ^a   Lee, Ju Hee ^a   Ham, Kyungrok ^b   Hong, Sungwoo ^b   Hong, Soon Sun ^a  

^a Inha University School of Medicine   (South Korea)

^b Korea Advanced Institute of Science and Technology (KAIST)   (South Korea)

Author keywords

Apoptosis; Breast cancer; MTOR; PI3K

Indexed keywords

2 MORPHOLINO 8 PHENYLCHROMONE; HS 104; MAMMALIAN TARGET OF RAPAMYCIN; N [5 [3 (5 METHYL 1,2,4 OXADIAZOL 3 YL)IMIDAZO[1,2 A]PYRIDIN 6 YL]PYRIDIN 3 YL]BENZENESULFONAMIDE; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PROTEIN KINASE B; TAMOXIFEN; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; BREAST CANCER; CELL CYCLE ARREST; CELL CYCLE G2 PHASE; CELL CYCLE M PHASE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG MECHANISM; DRUG STRUCTURE; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; TUMOR XENOGRAFT;

ANIMALS; APOPTOSIS; BLOTTING, WESTERN; BREAST NEOPLASMS; CELL CYCLE CHECKPOINTS; CELL LINE, TUMOR; CELL PROLIFERATION; ENZYME INHIBITORS; FEMALE; FLUORESCENT ANTIBODY TECHNIQUE; HUMANS; IMIDAZOLES; IMMUNOENZYME TECHNIQUES; MICE; MICE, INBRED BALB C; MICE, NUDE; PHOSPHATIDYLINOSITOL 3-KINASE; PYRIDINES; SIGNAL TRANSDUCTION;

EID: 84857140273     PISSN: 03043835     EISSN: 18727980     Source Type: Journal    
DOI: 10.1016/j.canlet.2011.12.001     Document Type: Article

References (28)

1. Weigelt B., Peterse J.L., van 't Veer L.J. Breast cancer metastasis: markers and models. Nat. Rev. Cancer 2005, 5:591-602.
2. Jemal A., Siegel R., Xu J., Ward E. Cancer statistics, 2010. CA Cancer J. Clin. 2010, 60:277-300.
3. Vanhaesebroeck B., Guillermet-Guibert J., Graupera M., Bilanges B. The emerging mechanisms of isoform-specific PI3K signalling. Nat. Rev. Mol. Cell Biol. 2010, 11:329-341.
4. Saal L.H., Holm K., Maurer M., Memeo L., Su T., Wang X., Yu J.S., Malmstrom P.O., Mansukhani M., Enoksson J., Hibshoosh H., Borg A., Parsons R. PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma. Cancer Res. 2005, 65:2554-2559.
5. Kalinsky K., Jacks L.M., Heguy A., Patil S., Drobnjak M., Bhanot U.K., Hedvat C.V., Traina T.A., Solit D., Gerald W., Moynahan M.E. PIK3CA mutation associates with improved outcome in breast cancer. Clin. Cancer Res. 2009, 15:5049-5059.
6. Li J., Yen C., Liaw D., Podsypanina K., Bose S., Wang S.I., Puc J., Miliaresis C., Rodgers L., McCombie R., Bigner S.H., Giovanella B.C., Ittmann M., Tycko B., Hibshoosh H., Wigler M.H., Parsons R. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 1997, 275:1943-1947.
7. Saal L.H., Johansson P., Holm K., Gruvberger-Saal S.K., She Q.B., Maurer M., Koujak S., Ferrando A.A., Malmstrom P., Memeo L., Isola J., Bendahl P.O., Rosen N., Hibshoosh H., Ringner M., Borg A., Parsons R. Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity. Proc. Natl. Acad. Sci. USA 2007, 104:7564-7569.
8. Stemke-Hale K., Gonzalez-Angulo A.M., Lluch A., Neve R.M., Kuo W.L., Davies M., Carey M., Hu Z., Guan Y., Sahin A., Symmans W.F., Pusztai L., Nolden L.K., Horlings H., Berns K., Hung M.C., van de Vijver M.J., Valero V., Gray J.W., Bernards R., Mills G.B., Hennessy B.T. An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer. Cancer Res. 2008, 68:6084-6091.
9. Slamon D.J., Clark G.M., Wong S.G., Levin W.J., Ullrich A., McGuire W.L. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987, 235:177-182.
10. Holbro T., Beerli R.R., Maurer F., Koziczak M., Barbas C.F., Hynes N.E. The ErbB2/ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation. Proc. Natl. Acad. Sci. USA 2003, 100:8933-8938.
11. Lopez-Knowles E., O'Toole S.A., McNeil C.M., Millar E.K., Qiu M.R., Crea P., Daly R.J., Musgrove E.A., Sutherland R.L. PI3K pathway activation in breast cancer is associated with the basal-like phenotype and cancer-specific mortality. Int. J. Cancer 2010, 126:1121-1131.
12. Chresta C.M., Davies B.R., Hickson I., Harding T., Cosulich S., Critchlow S.E., Vincent J.P., Ellston R., Jones D., Sini P., James D., Howard Z., Dudley P., Hughes G., Smith L., Maguire S., Hummersone M., Malagu K., Menear K., Jenkins R., Jacobsen M., Smith G.C., Guichard S., Pass M. AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity. Cancer Res. 2010, 70:288-298.
13. 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., Shuttleworth S.J. 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, 51:5522-5532.
14. Hirai H., Sootome H., Nakatsuru Y., Miyama K., Taguchi S., Tsujioka K., Ueno Y., Hatch H., Majumder P.K., Pan B.S., Kotani H. MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo. Mol. Cancer Ther. 2010, 9:1956-1967.
15. Maira S.M., Stauffer F., Brueggen J., Furet P., Schnell C., Fritsch C., Brachmann S., Chene P., De Pover A., Schoemaker K., Fabbro D., Gabriel D., Simonen M., Murphy L., Finan P., Sellers W., Garcia-Echeverria 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, 7:1851-1863.
16. Kim O., Jeong Y., Lee H., Hong S.S., Hong S. Design and synthesis of imidazopyridine analogues as inhibitors of phosphoinositide 3-kinase signaling and angiogenesis. J. Med. Chem. 2011, 54:2455-2466.
17. Huang C.H., Mandelker D., Schmidt-Kittler O., Samuels Y., Velculescu V.E., Kinzler K.W., Vogelstein B., Gabelli S.B., Amzel L.M. The structure of a human p110alpha/p85alpha complex elucidates the effects of oncogenic PI3Kalpha mutations. Science 2007, 318:1744-1748.
18. Morris G.M., Goodsell D.S., Halliday R.S., Huey R., Hart W.E., Belew R.K., Olson A.J. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem. 1998, 19:1639-1662.
19. Dowling R.J., Topisirovic I., Alain T., Bidinosti M., Fonseca B.D., Petroulakis E., Wang X., Larsson O., Selvaraj A., Liu Y., Kozma S.C., Thomas G., Sonenberg N. mTORC1-mediated cell proliferation, but not cell growth, controlled by the 4E-BPs. Science 2010, 328:1172-1176.
20. Ikeda S., Kishida S., Yamamoto H., Murai H., Koyama S., Kikuchi A. Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin. EMBO J. 1998, 17:1371-1384.
21. Hirose Y., Katayama M., Mirzoeva O.K., Berger M.S., Pieper R.O. Akt activation suppresses Chk2-mediated, methylating agent-induced G2 arrest and protects from temozolomide-induced mitotic catastrophe and cellular senescence. Cancer Res. 2005, 65:4861-4869.
22. Liang J., Slingerland J.M. Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression. Cell. Cycle 2003, 2:339-345.
23. Katayama K., Fujita N., Tsuruo T. Akt/protein kinase B-dependent phosphorylation and inactivation of WEE1Hu promote cell cycle progression at G2/M transition. Mol. Cell. Biol. 2005, 25:5725-5737.
24. Franke T.F., Hornik C.P., Segev L., Shostak G.A., Sugimoto C. PI3K/Akt and apoptosis: size matters. Oncogene 2003, 22:8983-8998.
25. Gajewski T.F., Thompson C.B. Apoptosis meets signal transduction: elimination of a BAD influence. Cell 1996, 87:589-592.
26. Zha J., Harada H., Yang E., Jockel J., Korsmeyer S.J. Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L). Cell 1996, 87:619-628.
27. Pap M., Cooper G.M. Role of glycogen synthase kinase-3 in the phosphatidylinositol 3-Kinase/Akt cell survival pathway. J. Biol. Chem. 1998, 273:19929-19932.
28. Hu L., Zaloudek C., Mills G.B., Gray J., Jaffe R.B. In vivo and in vitro ovarian carcinoma growth inhibition by a phosphatidylinositol 3-kinase inhibitor (LY294002). Clin. Cancer Res. 2000, 6:880-886.