HS-173, a novel phosphatidylinositol 3-kinase (PI3K) inhibitor, has anti-tumor activity through promoting apoptosis and inhibiting angiogenesis

Cancer Letters

Volumn 328, Issue 1, 2013, Pages 152-159

  Lee, Hyunseung ^a   Jung, Kyung Hee ^a   Jeong, Yujeong ^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

Angiogenesis; Anti cancer drug; Apoptosis; PI3K inhibitor

Indexed keywords

ETHYL 6 [5 (PHENYLSULFONAMIDO)PYRIDIN 3 YL]IMIDAZOL [1,2 A]PYRIDINE 3 CARBOXYLATE; HS 173; HYPOXIA INDUCIBLE FACTOR 1ALPHA; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; UNCLASSIFIED DRUG; VASCULOTROPIN;

ANGIOGENESIS; ANIMAL CELL; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; BREAST CANCER; CANCER CELL; CELL CYCLE ARREST; CELL CYCLE G2 PHASE; CELL CYCLE M PHASE; CELL MIGRATION; CONTROLLED STUDY; DRUG STRUCTURE; HUMAN; HUMAN CELL; IN VITRO STUDY; LIVER CANCER; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION;

ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; CELL LINE, TUMOR; HUMANS; MALE; MICE; MICE, INBRED BALB C; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; PHOSPHATIDYLINOSITOL 3-KINASE; PYRIDINES; SULFONAMIDES;

MUS;

EID: 84868484417     PISSN: 03043835     EISSN: 18727980     Source Type: Journal    
DOI: 10.1016/j.canlet.2012.08.020     Document Type: Article

References (39)

1. Cantley L.C., Auger K.R., Carpenter C., Duckworth B., Graziani A., Kapeller R., Soltoff S. Oncogenes and signal transduction. Cell 1991, 64:281-302.
2. Jia S., Roberts T.M., Zhao J.J. Should individual PI3 kinase isoforms be targeted in cancer?. Curr. Opin. Cell Biol. 2009, 21:199-208.
3. Kaplan D.R., Whitman M., Schaffhausen B., Pallas D.C., White M., Cantley L., Roberts T.M. Common elements in growth factor stimulation and oncogenic transformation: 85kd phosphoprotein and phosphatidylinositol kinase activity. Cell 1987, 50:1021-1029.
4. Whitman M., Kaplan D.R., Schaffhausen B., Cantley L., Roberts T.M. Association of phosphatidylinositol kinase activity with polyoma middle-T competent for transformation. Nature 1985, 315:239-242.
5. Sugimoto Y., Whitman M., Cantley L.C., Erikson R.L. Evidence that the Rous sarcoma virus transforming gene product phosphorylates phosphatidylinositol and diacylglycerol. Proc. Natl. Acad. Sci. USA 1984, 81:2117-2121.
6. 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.
7. Engelman J.A., Luo J., Cantley L.C. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat. Rev. Genet. 2006, 7:606-619.
8. Lee J.W., Soung Y.H., Kim S.Y., Lee H.W., Park W.S., Nam S.W., Kim S.H., Lee J.Y., Yoo N.J., Lee S.H. PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomas. Oncogene 2005, 24:1477-1480.
9. Broderick D.K., Di C., Parrett T.J., Samuels Y.R., Cummins J.M., McLendon R.E., Fults D.W., Velculescu V.E., Bigner D.D., Yan H. Mutations of PIK3CA in anaplastic oligodendrogliomas, high-grade astrocytomas, and medulloblastomas. Cancer Res. 2004, 64:5048-5050.
10. Bachman K.E., Argani P., Samuels Y., Silliman N., Ptak J., Szabo S., Konishi H., Karakas B., Blair B.G., Lin C., Peters B.A., Velculescu V.E., Park B.H. The PIK3CA gene is mutated with high frequency in human breast cancers. Cancer Biol. Ther. 2004, 3:772-775.
11. Vogt P.K., Kang S., Elsliger M.A., Gymnopoulos M. Cancer-specific mutations in phosphatidylinositol 3-kinase. Trends Biochem. Sci. 2007, 32:342-349.
12. J.J. Zhao, T.M. Roberts, PI3 kinases in cancer: from oncogene artifact to leading cancer target. Sci. STKE (2006) pe52.
13. Workman P., Clarke P.A., Guillard S., Raynaud F.I. Drugging the PI3 kinome. Nat. Biotechnol. 2006, 24:794-796.
14. Shaw R.J., Cantley L.C. Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature 2006, 441:424-430.
15. 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.
16. 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.
17. 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.
18. 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.
19. Lee H., Li G.Y., Jeong Y., Jung K.H., Lee J.H., Ham K., Hong S., Hong S.S. A novel imidazopyridine analogue as a phosphatidylinositol 3-kinase inhibitor against human breast cancer. Cancer Lett. 2012, 318:68-75.
20. 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.
21. 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.
22. 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.
23. Gautier J., Solomon M.J., Booher R.N., Bazan J.F., Kirschner M.W. Cdc25 is a specific tyrosine phosphatase that directly activates p34cdc2. Cell 1991, 67:197-211.
24. Gu Y., Rosenblatt J., Morgan D.O. Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15. EMBO J. 1992, 11:3995-4005.
25. Strausfeld U., Labbe J.C., Fesquet D., Cavadore J.C., Picard A., Sadhu K., Russell P., Doree M. Dephosphorylation and activation of a p34cdc2/cyclin B complex in vitro by human CDC25 protein. Nature 1991, 351:242-245.
26. Carnero A., Blanco-Aparicio C., Renner O., Link W., Leal J.F. The PTEN/PI3K/AKT signalling pathway in cancer, therapeutic implications. Curr. Cancer Drug Targets 2008, 8:187-198.
27. Yang L., Dan H.C., Sun M., Liu Q., Sun X.M., Feldman R.I., Hamilton A.D., Polokoff M., Nicosia S.V., Herlyn M., Sebti S.M., Cheng J.Q. Akt/protein kinase B signaling inhibitor-2, a selective small molecule inhibitor of Akt signaling with antitumor activity in cancer cells overexpressing Akt. Cancer Res. 2004, 64:4394-4399.
28. Workman P. Inhibiting the phosphoinositide 3-kinase pathway for cancer treatment. Biochem. Soc. Trans. 2004, 32:393-396.
29. Schultz R.M., Merriman R.L., Andis S.L., Bonjouklian R., Grindey G.B., Rutherford P.G., Gallegos A., Massey K., Powis G. In vitro and in vivo antitumor activity of the phosphatidylinositol-3-kinase inhibitor, wortmannin. Anticancer Res. 1995, 15:1135-1139.
30. Rowinsky E.K. Targeting the molecular target of rapamycin (mTOR). Curr. Opin. Oncol. 2004, 16:564-575.
31. Shamji A.F., Nghiem P., Schreiber S.L. Integration of growth factor and nutrient signaling: implications for cancer biology. Mol. Cell 2003, 12:271-280.
32. 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.
33. Cuddihy A.R., O'Connell M.J. Cell-cycle responses to DNA damage in G2. Int. Rev. Cytol. 2003, 222:99-140.
34. 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.
35. Wang X., Proud C.G. The mTOR pathway in the control of protein synthesis. Physiology (Bethesda) 2006, 21:362-369.
36. Ashe P.C., Berry M.D. Apoptotic signaling cascades. Prog. Neuropsychopharmacol. Biol. Psychiatry 2003, 27:199-214.
37. Belozerov V.E., Van Meir E.G. Hypoxia inducible factor-1: a novel target for cancer therapy. Anti-Cancer Drugs 2005, 16:901-909.
38. Zhong H., Chiles K., Feldser D., Laughner E., Hanrahan C., Georgescu M.M., Simons J.W., Semenza G.L. Modulation of hypoxia-inducible factor 1alpha expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics. Cancer Res. 2000, 60:1541-1545.
39. Mazure N.M., Chen E.Y., Laderoute K.R., Giaccia A.J. Induction of vascular endothelial growth factor by hypoxia is modulated by a phosphatidylinositol 3-kinase/Akt signaling pathway in Ha-ras-transformed cells through a hypoxia inducible factor-1 transcriptional element. Blood 1997, 90:3322-3331.