A vascular targeted pan phosphoinositide 3-kinase inhibitor prodrug, SF1126, with antitumor and antiangiogenic activity

Cancer Research

Volumn 68, Issue 1, 2008, Pages 206-215

  Garlich, Joseph R ^c   De, Pradip ^a   Dey, Nandini ^a   Jing, Dong Su ^c   Peng, Xiaodong ^c   Miller, Antoinette ^c   Murali, Ravoori ^d   Lu, Yiling ^d   Mills, Gordon B ^d   Kundra, Vikas ^d   Shu, H K ^b   Peng, Qiong ^a   Durden, Donald L ^a,b  

^a AFLAC   (United States)

^b EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c Semafore Pharmaceuticals Inc   (United States)

^d UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 MORPHOLINO 8 PHENYLCHROMONE; ANTINEOPLASTIC AGENT; INTEGRIN; PROTEIN KINASE B; SF 1101; SF 1126; SF 1326; UNCLASSIFIED DRUG; ANGIOGENESIS INHIBITOR; ARGINYL GLYCYL ASPARTYL SERINE; ARGINYL-GLYCYL-ASPARTYL-SERINE; CHROMONE DERIVATIVE; ENZYME INHIBITOR; OLIGOPEPTIDE; PHOSPHATIDYLINOSITOL 3 KINASE; PRODRUG;

ANIMAL EXPERIMENT; ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG ACCUMULATION; DRUG HALF LIFE; DRUG MECHANISM; DRUG SOLUBILITY; DRUG TOLERABILITY; FEMALE; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; TUMOR GROWTH; ANIMAL; CELL PROLIFERATION; CHEMISTRY; DRUG ANTAGONISM; DRUG EFFECT; DRUG SCREENING; ENZYMOLOGY; METABOLISM; MOUSE STRAIN; NEOPLASM; NEOVASCULARIZATION (PATHOLOGY); TUMOR CELL LINE; VASCULARIZATION;

1-PHOSPHATIDYLINOSITOL 3-KINASE; ANGIOGENESIS INHIBITORS; ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CELL PROLIFERATION; CHROMONES; ENZYME INHIBITORS; HUMANS; MICE; MICE, INBRED STRAINS; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; OLIGOPEPTIDES; PRODRUGS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 39149123820     PISSN: 00085472     EISSN: None     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-07-0669     Document Type: Article

References (39)

1. Vlahos CJ, Matter WF, Hui KY, Brown RF. A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). J Biol Chem 1994;269:5241-8.
2. Camps M, Ruckle T, Ji H, et al. Blockade of PI3Kγ suppresses joint inflammation and damage in mouse models of rheumatoid arthritis. Nat Med 2005;11:936-43.
3. Hayakawa M, Kaizawa H, Moritomo H, et al. Synthesis and biological evaluation of 4-morpholino-2-phenylquinazolines and related derivatives as novel PI3 kinase p110α inhibitors. Bioorg Med Chem 2006;14:6847-58.
4. Nutley BP, Raynaud FI, Hayes A, Goddard P, Jarman M, Workman P. Pharmacokinetics and metabolism of the phospatidylinositol 3-kinase inhibitor LY294002 in the mouse [abstract #2044]. Proc Am Assoc Cancer Res 92nd Annu Meet 2001;92:380.
5. Hu L, Zaloudek C, Mills GB, Gray J, Jaffe RB. In vivo and in vitro ovarian carcinoma growth inhibition by a phosphatidylinositol 3-kinase inhibitor (LY294002). Clin Cancer Res 2000;6:880-6.
6. Su JD, Mayo LD, Donner DB, Durden DL. PTEN and phosphatidylinositol 3′-kinase inhibitors up-regulate p53 and block tumor-induced angiogenesis: evidence for an effect on the tumor and endothelial compartment. Cancer Res 2003;63:3585-92.
7. Castellino RC and Durden DL. PTEN/PI-3 kinase signaling node: An intercept point for the control of angiogenesis. Nat Clin Pract Neurol. In press. 2007.
8. Katso R, Okkenhaug K, Ahmadi K, White S, Timms J, Waterfield MD. Cellular function of phosphoinositide 3-kinases: implications for development, homeostasis, and cancer. Annu Rev Cell Dev Biol 2001;17:615-75.
9. Li B, Yuan M, Kim IA, Chang CM, Bernhard EJ, Shu HK. Mutant epidermal growth factor receptor displays increased signaling through the phosphatidylinositol-3 kinase/AKT pathway and promotes radioresistance in cells of astrocytic origin. Oncogene 2004;23:4594-602.
10. Tan C, de Noronha RG, Roecker AJ, et al. Identification of a novel small-molecule inhibitor of the hypoxia-inducible factor 1 pathway. Cancer Res 2005;65:605-12.
11. Dey N, Howell BW, De PK, Durden DL. CSK negatively regulates nerve growth factor induced neural differentiation and augments AKT kinase activity. Exp Cell Res 2005;307:1-14.
12. Wen S, Stolarov J, Myers MP, et al. PTEN controls tumor-induced angiogenesis. Proc Natl Acad Sci U S A 2001;98:4622-7.
13. Sheehan KM, Calvert VS, Kay EW, et al. Use of reverse phase protein microarrays and reference standard development for molecular network analysis of metastatic ovarian carcinoma. Mol Cell Proteomics 2005;4:346-55.
14. Wong AJ, Ruppert JM, Bigner SH, et al. Structural alterations of the epidermal growth factor receptor gene in human gliomas. Proc Natl Acad Sci U S A 1992;89:2965-9.
15. Kanzaki M, Furukawa M, Raab W, Pessin JE. Phosphatidylinositol 4,5-bisphosphate regulates adipocyte actin dynamics and GLUT4 vesicle recycling. J Biol Chem 2004;279:30622-33.
16. Mills GB, Lu Y, Kohn EC. Linking molecular therapeutics to molecular diagnostics: inhibition of the FRAP/RAFT/TOR component of the PI3K pathway preferentially blocks PTEN mutant cells in vitro and in vivo. Proc Natl Acad Sci U S A 2001;98:10031-3.
17. Wendel HG, Malina A, Zhao Z, et al. Determinants of sensitivity and resistance to rapamycin-chemotherapy drug combinations in vivo. Cancer Res 2006;66:7639-46.
18. Evan GI. Can't kick that oncogene habit. Cancer Cell 2006;10:345-47.
19. Blancher C, Moore JW, Robertson N, Harris AL. Effects of ras and von Hippel-Lindau (VHL) gene mutations on hypoxia-inducible factor (HIF)-1α, HIF-2α, and vascular endothelial growth factor expression and their regulation by the phosphatidylinositol 3′-kinase/Akt signaling pathway. Cancer Res 2001;61:7349-55.
20. Zhong H, Chiles K, Feldser D, et al. Modulation of hypoxia-inducible factor 1α expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics [in process citation]. Cancer Res 2000;60:1541-5.
21. Huang J, Kontos CD. PTEN modulates vascular endothelial growth factor-mediated signaling and angiogenic effects. J Biol Chem 2002;277:10760-6.
22. Hu L, Hofmann J, Lu Y, Mills GB, Jaffe RB. Inhibition of phosphatidylinositol 3′-kinase increases efficacy of paclitaxel in in vitro and in vivo ovarian cancer models. Cancer Res 2002;62:1087-92.
23. Mayo L, Donner D. The PTEN, Mdm2, p53 tumor suppressor-oncoprotein network. Trends Biochem Sci 2002;27:462-5.
24. Mayo LD, Dixon JE, Durden DL, Tonks NK, Donner DB. PTEN protects p53 from Mdm2 and sensitizes cancer cells to chemotherapy. J Biol Chem 2002;277:5484-9.
25. Mayo LD, Donner DB. A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus. Proc Natl Acad Sci U S A 2001;98:11598-603.
26. Gottschalk AR, Doan A, Nakamura JL, Haas-Kogan DA, Stokoe D. Inhibition of phosphatidylinositol-3-kinase causes cell death through a protein kinase B (PKB)-dependent mechanism and growth arrest through a PKB-independent mechanism. Int J Radiat Oncol Biol Phys 2005;61:1183-8.
27. Gottschalk AR, Doan A, Nakamura JL, Stokoe D, Haas-Kogan DA. Inhibition of phosphatidylinositol-3-kinase causes increased sensitivity to radiation through a PKB-dependent mechanism. Int J Radiat Oncol Biol Phys 2005;63:1221-7.
28. Nakamura JL, Karlsson A, Arvold ND, et al. PKB/Akt mediates radiosensitization by the signaling inhibitor LY294002 in human malignant gliomas. J Neurooncol 2005;71:215-22.
29. Ozes ON, Mayo LD, Gustin JA, Pfeffer SR, Pfeffer LM, Donner DB. NF-κB activation by tumour necrosis factor requires the Akt serine-threonine kinase [see comments]. Nature 1999;401:82-5.
30. Goswami A, Burikhanov R, de Thonel A, et al. Binding and phosphorylation of par-4 by akt is essential for cancer cell survival. Mol Cell 2005;20:33-44.
31. Goswami A, Ranganathan P, Rangnekar VM. The phosphoinositide 3-kinase/Akt1/Par-4 axis: a cancer-selective therapeutic target. Cancer Res 2006;66:2889-92.
32. Inoki K, Li Y, Zhu T, Wu J, Guan KL. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol 2002;4:648-57.
33. Wanzel M, Kleine-Kohlbrecher D, Herold S, et al. Akt and 14-3-3eta regulate Miz1 to control cell-cycle arrest after DNA damage. Nat Cell Biol 2005;7:30-41.
34. King AJ, Sun H, Diaz B, et al. The protein kinase Pak3 positively regulates Raf-1 activity through phosphorylation of serine 338. Nature 1998;396:180-3.
35. Medema RH, Kops GJ, Bos JL, Burgering BM. AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1. Nature 2000;404:782-7.
36. Zhang L, Chen J, Fu H. Suppression of apoptosis signal-regulating kinase 1-induced cell death by 14-3-3 proteins. Proc Natl Acad Sci U S A 1999;96:8511-5.
37. Fujita N, Sato S, Katayama K, Tsuruo T. Akt-dependent phosphorylation of p27Kip1 promotes binding to 14-3-3 and cytoplasmic localization. J Biol Chem 2002;277:28706-13.
38. Thomas SM, Grandis JR. Pharmacokinetic and pharmacodynamic properties of EGFR inhibitors under clinical investigation. Cancer Treat Rev 2004;30:255-68.
39. Cantley LC, Neel BG. New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc Natl Acad Sci U S A 1999;96:4240-5.