The development of phosphatidylinositol ether lipid analogues as inhibitors of the serine/threonine kinase, Akt

Expert Opinion on Investigational Drugs

Volumn 13, Issue 7, 2004, Pages 787-797

  Gills, Joell J ^a   Dennis, Phillip A ^a  

^a NATIONAL NAVAL MEDICAL CENTER   (United States)

Author keywords

Akt; Cancer; Phosphatidylinositol ether lipid analogue; Pleckstrin homology domain

Indexed keywords

ANTINEOPLASTIC AGENT; CYTARABINE; ETHER PHOSPHOLIPID; ETOPOSIDE; INTEGRIN; PHOSPHATIDYLINOSITOL; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PROTEIN KINASE INHIBITOR; PROTEIN SERINE THREONINE KINASE; PROTEIN TYROSINE KINASE; RAS PROTEIN; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND;

APOPTOSIS; CANCER CELL CULTURE; CANCER CHEMOTHERAPY; CARCINOGENESIS; CELL SURVIVAL; DRUG ACTIVITY; DRUG SELECTIVITY; DRUG SENSITIZATION; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME PHOSPHORYLATION; HUMAN; NONHUMAN; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; ENZYME INHIBITORS; HUMANS; PHOSPHATIDYLINOSITOLS; PHOSPHOLIPID ETHERS; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-AKT;

EID: 3543117821     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.13.7.787     Document Type: Review

References (59)

1. COFFER PJ, JIN J, WOODGETT JR: Protein kinase B (c-Akt): a multifunctional mediator of phosphatidylinositol 3-kinase activation. Biochem. J. (1998) 335(Pt 1):1-13.
2. ZINDA MJ, JOHNSON MA, PAUL JD et al.: AKT-1, -2, and -3 are expressed in both normal and tumor tissues of the lung, breast, prostate, and colon. Clin. Cancer Res. (2001) 7(8):2475-2479.
3. HEWITT S, YANG X, STEINBERG X, SWAIN SM, DENNIS PA: In situ analysis of the PI3K/Akt pathway in normal and cancerous tissues on human multi-tissue arrays. (Submitted).
4. ERMOIAN RP, FURNISS CS, LAMBORN KR et al.: Dysregulation of PTEN and protein kinase B is associated with glioma histology and patient survival. Clin. Cancer Res. (2002) 8(5):1100-1106.
5. PEREZ-TENORIO G, STAL O: Activation of AKT/PKB in breast cancer predicts a worse outcome among endocrine treated patients. Br. J. Cancer (2002) 86(4):540-545.
6. TSAO AS, McDONNELL T, LAM S et al.: Increased phospho-AKT (Ser(473)) expression in bronchial dysplasia: implications for lung cancer prevention studies. Cancer Epidemiol. Biomarkers Prev. (2003) 12(7):660-664.
7. ROY HK, OLUSOLA BF, CLEMENS DL et al.: AKT proto-oncogene overexpression is an early event during sporadic colon carcinogenesis. Carcinogenesis (2002) 23(1):201-205.
8. STAAL SP: Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2: amplification of AKT1 in a primary human gastric adenocarcinoma. Proc. Natl. Acad. Sci. USA (1987) 84(14):5034-5037.
9. RUGGERI BA, HUANG L, WOOD M, CHENG JQ, TESTA JR: Amplification and overexpression of the AKT2 oncogene in a subset of human pancreatic ductal adenocarcinomas. Mol. Carcinog. (1998) 21(2):81-86.
10. BELLACOSA A, DE FEO D, GODWIN AK et al.: Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas. Int. J. Cancer (1995) 64(4):280-285.
11. SHAYESTEH L, LU Y, KUO WL et al.: PIK3CA is implicated as an oncogene in ovarian cancer. Nat. Genet. (1999) 21(1):99-102.
12. MA YY, WEI SJ, LIN YC et al.: PIK3CA as an oncogene in cervical cancer. Oncogene (2000) 19(23):2739-2744.
13. VIVANCO I, SAWYERS CL: The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat. Rev. Cancer (2002) 2(7):489-501.
14. 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. USA (1999) 96(8):4240-4245.
15. STAMBOLIC V, TSAO MS, MACPHERSON D, SUZUKI A, CHAPMAN WB, MAK TW: High incidence of breast and endometrial neoplasia resembling human Cowden syndrome in PTEN ± mice. Cancer Rks. (2000) 60(13 ):3605-3611.
16. CLARK AS, WEST K, STREICHER S, DENNIS PA: Constitutive and inducible Akt activity promotes resistance to chemotherapy, trastuzumab, or tamoxifen in breast cancer cells. Mol. Cancer Ther. (2002) 1(9):707-717.
17. BROGNARD J, CLARK AS, NI Y, DENNIS PA: Akt/protein kinase B is constitutively active in non-small cell lung cancer cells and promotes cellular survival and resistance to chemotherapy and radiation. Cancer Res. (2001) 61(10):3986-3997.
18. WEST KA, BROGNARD J, CLARK AS et al.: Rapid Akt activation by nicotine and a tobacco carcinogen modulates the phenotype of normal human airway epithelial cells. J. Clin. Invest. (2003) 111(1):81-90.
19. BURDICK AD, DAVIS JW 2nd, LIU KJ et al.: Benzo(a)pyrene quinones increase cell proliferation, generate reactive oxygen species, and transactivate the epidermal growth factor receptor in breast epithelial cells. Cancer Res. (2003) 63(22):7825-7833.
20. SEGRELLES C, RUIZ S, PEREZ P et al.: Functional roles of Akt signaling in mouse skin tumorigenesis. Oncogene (2002) 21(1):53-64.
21. SOUZA K, MADDOCK DA, ZHANG Q et al.: Arsenite activation of P13K/AKT cell survival pathway is mediated by p38 in cultured human keratinocytes. Mol. Med. (2001) 7(11):767-772.
22. MANNING G, WHYTE DB, MARTINEZ R, HUNTER T, SUDARSANAM S: The protein kinase complement of the human genome. Science (2002) 298(5600):1912-1934.
23. LEMMON MA, FERGUSON KM, ABRAMS CS: Pleckstrin homology domains and the cytoskeleton. FEBS Lett. (2002) 513(1):71-76.
24. BALENDRAN A, CASAMAYOR A, DEAK M et al.: PDK1 acquires PDK2 activity in the presence of a synthetic peptide derived from the carboxyl terminus of PRK2. Curr. Biol. (1999) 9(8):393-404.
25. DELCOMMENNE M, TAN C, GRAY V, RUE L, WOODGETT J, DEDHAR S: Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase. Proc. Natl. Acad. Sci. USA (1998) 95(19):11211-11216.
26. LYNCH DK, ELLIS CA, EDWARDS PA, HILES ID: Integrin-linked kinase regulates phosphorylation of serine 473 of protein kinase B by an indirect mechanism. Oncogene (1999) 18(56):8024-8032.
27. TOKER A, NEWTON AC: Akt/protein kinase B is regulated by autophosphorylation at the hypothetical PDK-2 site. J. Biol. Chem. (2000) 275(12):8271-8274.
28. HILL MM, FENG J, HEMMINGS BA: Identification of a plasma membrane Raft-associated PKB Ser473 kinase activity that is distinct from ILK and PDK1. Curr. Biol. (2002) 12(14):1251-1255.
29. FILIPPA N, SABLE CL, FILLOUX C, HEMMINGS B, VAN OBBERGHEN E: Mechanism of protein kinase B activation by cyclic AMP-dependent protein kinase. Mol. Cell. Biol. (1999) 19(7):4989-5000.
30. YANO S, TOKUMITSU H, SODERLING TR: Calcium promotes cell survival through CaM-K kinase activation of the protein-kinase-B pathway. Nature (1998) 396(6711):584-587.
31. POWELL DJ, HAJDUCH E, KULAR G, HUNDAL HS: Ceramide disables 3-phosphoinositide binding to the pleckstrin homology domain of protein kinase B (PKB)/Akt by a PKCzeta-dependent mechanism. Mol. Cell. Biol. (2003) 23(21):7794-7808.
32. CONUS NM, HANNAN KM, CRISTIANO BE, HEMMINGS BA, PEARSON RB: Direct identification of tyrosine 474 as a regulatory phosphorylation site for the Akt protein kinase. J. Biol. Chem. (2002) 277(41):38021-38028.
33. BASSO AD, SOLIT DB, CHIOSIS G, GIRI B, TSICHLIS P, ROSEN N: Akt forms an intracellular complex with Hsp90 and Cdc37 and is destabilized by inhibitors of Hsp90 function. J. Biol. Chem. (2002) 277(4):39858-39866.
34. PEKARSKY Y, KOVAL A, HALLAS C et al.: Tcl1 enhances Akt kinase activity and mediates its nuclear translocation. Proc. Natl. Acad. Sci. USA (2000) 97(7):3028-3033.
35. BRAZIL DP, PARK J, HEMMINGS BA: PKB binding proteins. Getting in on the Akt. Cell (2002) 111(3):293-303.
36. DU K, HERZIG S, KULKARNI RN, MONTMINY M: TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver. Science (2003) 300(5625):1574-1577.
37. POWIS G, AKSOY IA, MELDER DC et al.: D-3-deoxy-3-substituted myo-inositol analogues as inhibitors of cell growth. Cancer Chemother. Pharmacol. (1991) 29(2):95-104.
38. ANTONSSON B: Phosphatidylinositol synthase from mammalian tissues. Biochim. Biophys. Acta (1997) 1348(1-2):179-186.
39. KOZIKOWSKI AP, KIDDLE JJ, FREW T, BERGGREN M, POWIS G: Synthesis and biology of 1D-3-deoxyphosphatidylinositol: a putative antimetabolite of phosphatidylinositol-3-phosphate and an inhibitor of cancer cell colony formation. J. Med. Chem. (1995) 38(7):1053-1056.
40. QIAO L, NAN F, KUNKEL M, GALLEGOS A, POWIS G, KOZIKOWSKI AP: 3-Deoxy-D-myo-inositol 1-phosphate, 1-phosphonate, and ether lipid analogues as inhibitors of phosphatidylinositol-3-kinase signaling and cancer cell growth. J. Med. Chem. (1998) 41(18):3303-3306.
41. HU Y, QIAO L, WANG S et al.: 3-(Hydroxymethyl)-bearing phosphatidylinositol ether lipid analogues and carbonate surrogates block PI3-K, Akt, and cancer cell growth. J. Med. Chem. (2000) 43(16):3045-3051.
42. MEUILLET EJ, MAHADEVAN D, VANKAYALAPATI H et al.: Specific inhibition of the Akt1 pleckstrin homology domain by D-3-deoxy-phosphatidyl-myo-inositol analogues. Mol. Cancer Ther. (2003) 2(4):389-399.
43. RONG SB, HU Y, ENYEDY I et al.: Molecular modeling studies of the Akt PH domain and its interaction with phosphoinositides. J. Med. Chem. (2001) 44(6):898-908.
44. HONDAL RJ, ZHAO Z, KRAVCHUK AV et al.: Mechanism of phosphatidylinositol-specific phospholipase C: a unified view of the mechanism of catalysis. Biochemistry (1998) 37(13):4568-4580.
45. KOZIKOWSKI AP, SUN H, BROGNARD J, DENNIS PA: Novel PI analogues selectively block activation of the pro-survival serine/threonine kinase Akt. J. Am. Chem. Soc. (2003) 125(5):1144-1145.
46. CASTILLO SS, BROGNARD J, PETUKHOV PA et al.: Preferential inhibition of Akt and killing of Akt-dependent cancer cells by rationally designed phosphatidylinositol ether lipid analogues. Cancer Res. (2004) 64:2782-2792.
47. MILBURN CC, DEAK M, KELLY SM, PRICE NC, ALESSI DR, VAN AALTEN DM: Binding of phosphatidylinositol 3,4,5-trisphosphate to the pleckstrin homology domain of protein kinase B induces a conformational change. Biochem. J. (2003) 375(Pt 3):531-538.
48. WEST KA, LINNOILA IR, BELINSKY SA, HARRIS CC, DENNIS PA: Tobacco carcinogen-induced cellular transformation increases activation of the phosphatidylinositol 3′-kinase/Akt pathway in vitro and in vivo. Cancer Res. (2004) 64(2):446-451.
49. MARTELLI AM, TAZZARI PL, TABELLINI G et al.: A new selective AKT pharmacological inhibitor reduces resistance to chemotherapeutic drugs, TRAIL, alltrans-retinoic acid, and ionizing radiation of human leukemia cells. Leukemia (2003) 17(9):1794-1805.
50. WEST KA, CASTILLO SS, DENNIS PA: Activation of the PI3K/Akt pathway and chemotherapeutic resistance. Drug Resist. Updat. (2002) 5(6):234-248.
51. GUO M, JOIAKIM A, REINERS JJ Jr: Suppression of 2,3,7,8-tetrachlorodibenzop-dioxin (TCDD)-mediated aryl hydrocarbon receptor transformation and CYP1A1 induction by the phosphatidylinositol 3-kinase inhibitor 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). Biochem. Pharmacol. (2000) 60(5):635-642.
52. DAVIES SP, REDDY H, CAIVANO M, COHEN P: Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem. J. (2000) 351(Pt 1):95-105.
53. REUVENI H, LIVNAH N, GEIGER T et al.: Toward a PKB inhibitor: modification of a selective PKA inhibitor by rational design. Biochemistry (2002) 41(32):10304-10314.
54. LUO Y, SMITH RA, GUAN R et al.: Pseudosubstrate peptides inhibit Akt and induce cell growth inhibition. Biochemistry (2004) 43(5):1254-1263.
55. JETZT A, HOWE JA, HORN MT et al.: Adenoviral-mediated expression of a kinase-dead mutant of Akt induces apoptosis selectively in tumor cells and suppresses tumor growth in mice. Cancer Res. (2003) 63(20):6697-6706.
56. HU Y, MEUILLET EJ, BERGGREN M, POWIS G, KOZIKOWSKI AP: 3-Deoxy-3-substituted-D-myo-inositol imidazolyl ether lipid phosphates and carbonate as inhibitors of the phosphatidylinositol 3-kinase pathway and cancer cell growth. Bioorg. Med. Chem. Lett (2001) 11(2):173-176.
57. 1 mice. Proc. Am. Assoc. Cancer Res. (2002) 43:604-605.
58. CHEN WS, XU PZ, GOTTLOB K et al.: Growth retardation and increased apoptosis in mice with homozygous disruption of the Akt1 gene. Genes Dev. (2001) 15(17):2203-2208.
59. CHO H, MU J, KIM JK et al.: Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB-β). Science (2001) 292(5522):1728-1731.