Isoform selective phosphoinositide 3-kinase γ and δ inhibitors and their therapeutic potential

Recent Patents on Inflammation and Allergy Drug Discovery

Volumn 2, Issue 1, 2008, Pages 1-10

  Ghigo, Alessandra ^a   Hirsch, Emilio ^a  

^a UNIVERSITY OF TURIN   (Italy)

Author keywords

Allergy; Asthma; COPD; Inflammation; PI3Ks; Rheumatoid arthritis

Indexed keywords

2 MORPHOLINO 8 PHENYLCHROMONE; 2,4 THIAZOLIDINEDIONE DERIVATIVE; 5 (6 QUINOXALINYLMETHYLENE) 2,4 THIAZOLIDINEDIONE; BENZOFURAN DERIVATIVE; BENZOTHIOPHENE DERIVATIVE; BENZOXAZINE DERIVATIVE; INDOLE DERIVATIVE; ISOENZYME; MORPHOLINE DERIVATIVE; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE ALPHA; PHOSPHATIDYLINOSITOL 3 KINASE BETA; PHOSPHATIDYLINOSITOL 3 KINASE DELTA; PHOSPHATIDYLINOSITOL 3 KINASE GAMMA; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PTERIDINE DERIVATIVE; PYRIMIDINE DERIVATIVE; QUINAZOLINONE DERIVATIVE; TG 100115; THIAZOLE DERIVATIVE; UNCLASSIFIED DRUG; WORTMANNIN;

ADAPTIVE IMMUNITY; ALLERGIC DISEASE; ARTICLE; CELL DIFFERENTIATION; CELL GROWTH; CELL METABOLISM; CELL MIGRATION; CELL PROLIFERATION; CELL SURVIVAL; CLINICAL TRIAL; DRUG POTENCY; DRUG SCREENING; DRUG SELECTIVITY; DRUG SPECIFICITY; DRUG TARGETING; ENZYME INHIBITION; ENZYME MECHANISM; ENZYME REGULATION; ENZYME SPECIFICITY; HUMAN; INFLAMMATORY DISEASE; INNATE IMMUNITY; LEUKOCYTE; NONHUMAN; PATENT; PRIORITY JOURNAL; PROTEIN EXPRESSION; UNSPECIFIED SIDE EFFECT;

1-PHOSPHATIDYLINOSITOL 3-KINASE; ANIMALS; DRUG DELIVERY SYSTEMS; ENZYME INHIBITORS; GENE EXPRESSION REGULATION, ENZYMOLOGIC; HUMANS; IMMUNE SYSTEM DISEASES; ISOENZYMES; MICE; PATENTS AS TOPIC;

EID: 42149105004     PISSN: 1872213X     EISSN: None     Source Type: Journal    
DOI: 10.2174/187221308783399270     Document Type: Article

References (76)

1. Vanhaesebroeck B, Leevers SJ, Ahmadi K, et al. Synthesis and function of 3-phosphorylated inositol lipids. Annu Rev Biochem 2001; 70: 535-602.
2. Engelman JA, Luo J, Cantley LC: The evolution of phosphatidy-linositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet 2006; 7(8): 606-619.
3. Hirsch E. Costa C. Ciraolo E. Phosphoinositide 3-kinases as a common platform for multi-hormone signaling. J Endocrinol 2007; 194(2): 243-256.
4. Wymann MP, Zvelebil M, Laffargue M. Phosphoinositide 3-kinase signaling-which way to target? Trends Pharmacol Sci 2003; 24(7): 366-376.
5. Stephens LR, Eguinoa A, Erdjument-Bromage H, et al. The G beta gamma sensitivity of a PI3K is dependent upon a tightly associated adaptor, p 101. Cell 1997; 89(1): 105-114.
6. Suire S, Coadwell J, Ferguson GJ, et al. p84, a new Gbetagamma-activated regulatory subunit of the type IB phosphoinositide 3-kinase p 110gamma. Curr Biol 2005; 15(6): 566-570.
7. Voigt P, Dorner MB, Schaefer M. Characterizatioin of p87PIKAP, a novel regulatory subunit of phosphoinositide 3-kinase gamma that is highly expressed in heart and interacts with PDE3B. J Biol Chem 2006; 281(15): 9977-9986.
8. Murga C, Fukuhara S, Gutkind JS. A novel role for phosphatidylinositol 3-kinase beta in signaling from G protein-coupled receptors to Akt. J Biol Chem 2000; 275(16): 12069-12073.
9. Cantley LC. The phosphoinositide 3-kinase pathway. Science 2002; 296(5573): 1655-1657.
10. Rohrschneider LR, Fuller JF, Wolf I, Liu Y, Lucas DM. Structure, function, and biology of SHIP proteins. Genes Dev 2000; 14(5): 505-520.
11. Wishart MJ, Dixon JE. PTEN and myotubularin phosphatases: from 3-phosphoinositide dephosphorylation to disease. Trends Cell Biol 2002; 12(12): 579-585.
12. Clayton E, Bardi G, Bell SE, et al. A crucial role for the p110 delta subunit of phosphatidylinositol 3-kinase in B cell development and activation. J Exp Med 2002; 196(6): 753-763.
13. Jou ST, Carpino N, Takahashi Y, et al. Essential, nonredundant role for the phosphoinositide 3-kinase p110delta in signaling by B-cell receptor complex. Mol Cell Biol 2002; 22(24): 8580-8591.
14. Okkenhaug K, Bilancio A, Farjot G, et al. Impaired B and T cell antigen receptor signaling in p110 delta PI 3-kinase mutant mice. Science 2002; 297(5583): 1031-1034.
15. Okkenhaug K, Patton DT, Bilancio A, et al. The p110 delta isoform of phosphoinositide 3-kinase controls clonal expansion and differentiation of Th cells. J Immunol 2006; 177(8): 5122-5128.
16. Gilfillan AM, Tkaczyk C. Integrated signalling pathways for mast-cell activation. Nat Rev Immunol 2006; 6(3):218-230.
17. Ali K, Bilancio A, Thomas M, et al. Essential role for the p110delta phosphoinositide 3-kinase in the allergic response. Nature 2004; 431(7011): 1007-1011.
18. Laffargue M, Calvez R, Finan P, et al. Phosphoinositide 3-kinase gamma is an essential amplifier of mast cell funcfion. Immunity 2002; 16(3): 441-451.
19. Hirsch E, Katanaev VL, Garlanda C, et al. Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation. Science 2000; 287(5455): 1049-1053.
20. Li Z, Jiang H, Xie W, et al. Roles of PLC-beta2 and -beta3 and PI3K gamma in chemoattractant-mediated signal transduction. Science 2000; 287(5455): 1046-1049.
21. Sasaki T, Irie-Sasaki J, Jones RG, et al. Function of PI3Kgamma in thymocyte development, T cell activation, and neutrophil migration. Science 2000; 287(5455): 1040-1046.
22. Iijima M, Devreotes P. Tumor suppressor PTEN mediates sensing of chemoattractant gradients. Cell 2002; 109(5): 599-610.
23. Funamoto S, Meili R, Lee S, Parry L, Firtel RA. Spatial and temporal regulation of 3-phosphoinositides by PI 3-kinase and PTEN mediates chemotaxis. Cell 2002; 109(5): 611-623.
24. Wang F, Herzmark P, Weiner OD, et al. Lipid products of PI(3)Ks maintain persistent cell polarity and directed motility in neutrophils. Nat Cell Biol 2002; 4(7): 513-518.
25. Weiner OD, Neilsen PO, Prestwich GD, et al. A PtdInsP(3)- and Rho GTPase-mediated positive feedback loop regulates neutrophil polarity. Nat Cell Biol 2002; 4(7): 509-513.
26. Costa C, Barberis L, Ambrogio C, et al. Negative feedback regulation of Rac in leukocytes from mice expressing a constitutively active phosphatidylinositol 3-kinase (gamma). Proc Natl Acad Sci U S A 2007; 104(36): 14354-14359.
27. Pinho V, Souza DG, Barsante MM, et al. Phosphoinositide-3 kinases critically regulate the recruitment and survival of eosinophils in vivo: importance for the resolution of allergic inflammation. J Leukoc Biol 2005; 77(5):800-810.
28. Del Prete A, Vermi W, Dander E, et al. Defective dendritic cell migration and activation of adaptive immunity in PI3Kgamma-deficient mice. Embo J 2004; 23(17): 3505-3515.
29. Jones GE, Prigmore E, Calvez R, et al. Requirement for PI3-kinase gamma in macrophage miotion to MCP-1 and CSF-1. Exp Cell Res 2003; 290(1): 129-131.
30. Reif K, Okkenhaug K, Sasaki T, et al. Cutting edge: differential roles for phosphoinositide 3-kinases, p110 gamma and p110 delta, in lymphocyte chemotaxis and homing. J Immunol 2004; 173(4): 2236-2240.
31. Arcaro A, Wymann MP. Wortmannin is a potent phosphatidylinositol 3-kinase inhibitor: the role of phosphatidylinositol 3,4,5-trisphosphate in neutrophil responses. Biochem J 1993; 296 (Pt 2): 297-301.
32. 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(7): 5241-5248.
33. Walker EH, Perisic O, Ried C, Stephens L, Williams RL. Structural insights into phosphoinositide 3-kinase catalysis and signaling. Nature 1999; 402: 313-320.
34. Walker EH, Pacold ME, Perisic O, et al. Structural determinants of phosphoinositide β-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine. Mol Cell 2000; 6(4): 909-919.
35. Brian PW, Curtis PJ, Hemming HG, Norris GLF. Wortmannin, an antibiotic produced by Penicillium wortmanni. Trans Br Mycol 1957; 40: 365-368.
36. Wymann MP, Bulgarelli-Leva G, Zvelebil MJ, et al. Wortmannin inactivates phosphoinositide 3-kinase by covalent modification of Lys-802, a residue involved in the phosphate transfer reaction. Mol Cell Biol 1996; 16(4): 1722-1733.
37. Robertson, A.D., Jackson, S.P., Kinche, D., Yaip, C., Prabaharan, H., Thompson, P.: WO01053266 (2001).
38. Garlich, J.R., Durden, D.L., Patterson, M., Su, J., Suhr, R.G.: US20056949537B2 (2005).
39. Raynaud FI, Eccles S, Clarke PA, et al. Pharmacologic characterization of a potent inhibitor of class I phosphatidylinositide 3-kinases. Cancer Res 2007; 67(12): 5840-5850.
40. Toledo LM, Lydon NB, Elbaum D. The structure-based design of ATP-site directed protein kinase inhibitors. Curr Med Chem 1999; 6(9): 775-805.
41. Garcia-Echeverria C, Traxler P, Evans DB. ATP site-directed competitive and irreversible inhibitors of protein kinases. Med Res Rev 2000;20(1): 28-57.
42. Ruckle T, Schwarz MK, Rommel C. PI3Kgamma inhibition: towards an 'aspirin of the 21st century'? Nat Rev Drug Discov 2006; 5(11): 903-918.
43. Jackson, S.P., Robertson, A.D., Kenche, D., Thompson, P., Prabaharan, H., Anderson, K., Abbott, B., Goncalves, I., Nesbitt, W., Schoenwaelder, S., Saylik, D.: WO04016607 (2004).
44. Sadhu, C., Dick, K., Treiberg, J., Sowell, C.G., Kesicki, E.A., Oliver, A.: WO01081346 (2001).
45. Fowler, K.W., Huang, D., Kesicki, E.A., Ooi, H.C., Oliver, A.R., Ruan, F., Treiberg, J., Puri, K.D.: WO05113556 (2005).
46. Sadhu, C., Dick, K., Treiberg, J., Sowell, C.G., Kesicki, E.A., Oliver, A.: WO03035075 (2003).
47. Shuttleworth, S.J., Folkes, A.J., Chuckowree, I.S., Wan, N.C., Hancox, T.C., Baker, S.J., Sohal, S., Latif, M.A.: WO06046035 (2006).
48. Bruce, I., Finan, P., Leblanc, C., McCarthy, C., Press, N.E., Bloomfield, G.C., Hayler, J., Kirman, L., Oza, M.S., Shukla, L.: WO03072557 (2003).
49. Wityak J, Das J, Moquin RV, et al. Discovery and initial SAR of 2-amino-5-carboxamidothiazoles as inhibitors of the Src-family kinasep56(Lck). Bioorg Med Chem Lett 2003, 13(22): 4007-4010.
50. Bloomfield, G.C., Bruce, I., Leblanc, C., Oza, M.S., Whitehead, L., Keller, T.H., Kirman, L., Mccarthy, C., Woodward, G.E.: WO04078754 ( 2004).
51. Bruce, I., Cuenoud, B., Pilgrim, G.E., Le Grand, D.M., Ritchie, C., Valade, B., Hayler, J., Budd, E.: WO04096797 (2004).
52. Bloomfield, G.C., Bruce, I., Hayler, J.F., Leblanc, C., Le Grand, D.M., McCarthy, C.: WO05021519 (2005).
53. Barvian, N.C., Kolz, C.N., Para, K.S., Patt, W.C., Visnick, M.: WO04052373 (2004).
54. Gogliotti, R.D., Muccioli, K.L., Para, K.S., Visnick, M.: WO04056820 ( 2004).
55. Para, K.S., Stankovic, C.J., Visnick, M.: WO04108708 (2004).
56. Gogliotti, R.D., Lee, H.T., Sexton, K.E., Visnick, M.: WO04108709 ( 2004).
57. Connolly, M.K., Gogliotti, R.D., Lee, H.T., Plummer, M.S., Sexton, K.E., Visnick, M.: WO04108713 (2004).
58. Bruendl, M.M., Connolly, M.K., Goodman, A.P., Gogliotti, R.D., Lee, H.T., Plummer, M.S., Sexton, K.E., Shahripour, A.B., Reichard, G., Visnick, M., Wilson, M.W.: WO04108715 (2004).
59. Connolly, M.K., Cogliotti, R.D., Hurt, C.R., Reichard, G., Visnick, M.: WO05023800 (2005).
60. Gogliotti, R.D., Lee, H.T., Sexton, K.E., Visnick, M.: WO04108716 ( 2004).
61. Gogliotti, R.D., Lee, H.T., Sexton, K.E., Visnick, M.: WO04108714 ( 2004).
62. Connolly, M.K., Gogliotti, R.D., Plummer, M.S., Visnick, M.: WO05042519 (2005).
63. Quattropani, A., Rueckle, T., Schwarz, M., Dorbais, J., Sauer, W., Cleva, C., Desforges, G.: WO05068444 (2005).
64. Rueckle, T., Jiang, X., Gaillard, P., Church, D., Vallotton, T.: WO04007491 (2004).
65. Rueckle, T., Shaw, J., Church, D., Covini, D.: WO05011686 (2005).
66. Rueckle, T., Quattropani, A., Pomel, V., Dorbais, J., Covini, D., Bischoff, A.: WO06024666 (2006).
67. Foukas LC, Claret M, Pearce W, et al. Critical role for the p110alpha phosphoinositide-3-OH kinase in growth and metabolic regulation. Nature 2006; 441(7091): 366-370.
68. Barber DF, Bartolome A, Hernandez C, et al. P13Kgamma inhibition blocks glomerulonephritis and extends lifespan in a mouse model of systemic lupus. Nat Med 2005; 11(9): 933-935.
69. Camps M, Ruckle T, Ji H, et al. Blockade of P13Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis. Nat Med 2005; 11(9): 936-943.
70. Firestein GS. Inhibiting inflammation in rheumatoid arthritis. N Engl J Med 2006; 354(1): 80-82.
71. Breitfelder, S., Maier, U., Brandl, T., Hoenke, C., Grauert, M., Pautsch, A., Hoffmann, M, Kalkbrenner, F., Joergensen, A., Schaenzle, G., Peters, S., Büttner, F., Bauer, E.: WO06040279 (2006).
72. Shimada, M., Murata, T., Fuchikami, K., Tsujishita, H., Omori, N., Kato, I., Miura, M., Urbahns, K., Gantner, F., Bacon, K.: WO04029055 (2004).
73. Diacovo, T.G., Hayflick, J.S., Puri, K.D.: WO06089106 (2006).
74. Puri KD, Doggett TA, Huang CY, et al. The role of endothelial P13Kgamma activity in neutrophil trafficking. Blood 2005; 106(1): 150-157.
75. Wrasidlo, W., Doukas, J., Royston, I., Noronha, G., Hood, J.D., Dneprovskaia, E., Gong, X., Splittgerber, U., Zhao, N.: WO04030635 (2004).
76. Doukas J, Wrasidlo W, Noronha G, et al. Phosphoinositide 3-kinase gamma/delta inhibition limits infarct size after myocardial ischemia/ reperfusion injury. Proc Natl Acad Sci USA 2006; 103(52): 19866-19871.