Highly selective MEK inhibitors

Current Enzyme Inhibition

Volumn 6, Issue 3, 2010, Pages 146-157

  Chih Shia, Lee ^a,b   Duesbery, Nicholas S ^a  

^a VAN ANDEL RESEARCH INSTITUTE   (United States)

^b MICHIGAN STATE UNIVERSITY   (United States)

Author keywords

Allosteric inhibition; Anthrax lethal toxin (LeTx); ARRY 142886 (AZD6244); MAPK ERK kinase (MEK); Mitogen activated protein kinase (MAPK); Mitogen activated protein kinase kinase (MKK); PD 184352 (CI 1040); Yersinia outer protein J (YopJ)

Indexed keywords

1,4 DIAMINO 1,4 BIS(2 AMINOPHENYLTHIO) 2,3 DICYANOBUTADIENE; 2 (2 AMINO 3 METHOXYPHENYL)CHROMONE; 2 (2 CHLORO 4 IODOANILINO) N CYCLOPROPYLMETHOXY 3,4 DIFLUOROBENZAMIDE; ANTHRAX TOXIN; ANTINEOPLASTIC AGENT; BACTERIAL TOXIN; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; MITOGEN ACTIVATED PROTEIN KINASE KINASE 4; MITOGEN ACTIVATED PROTEIN KINASE P38; N (2,3 DIHYDROXYPROPOXY) 3,4 DIFLUORO 2 (2 FLUORO 4 IODOANILINO)BENZAMIDE; RAF PROTEIN; SELUMETINIB; STRESS ACTIVATED PROTEIN KINASE; UNCLASSIFIED DRUG; YERSINIA OUTER PROTEIN J;

ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS; ADVANCED CANCER; ANTINEOPLASTIC ACTIVITY; ASTHENIA; BLURRED VISION; BREAST CANCER; CANCER CHEMOTHERAPY; CANCER INHIBITION; CANCER REGRESSION; CELL CYCLE ARREST; CELL CYCLE PROGRESSION; CELL PROLIFERATION; COLON CANCER; COLORECTAL CANCER; DIARRHEA; DRUG BINDING; DRUG CYTOTOXICITY; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG METABOLISM; DRUG SAFETY; DRUG SELECTIVITY; DRUG TARGETING; DRUG TOLERANCE; ENZYME ACTIVATION; ENZYME BLOOD LEVEL; ENZYME INHIBITION; FATIGUE; HALO EFFECT; HUMAN; IC 50; IN VITRO STUDY; KIDNEY CANCER; LUNG ADENOCARCINOMA; LUNG NON SMALL CELL CANCER; MAXIMUM TOLERATED DOSE; MELANOMA; MULTIPLE CYCLE TREATMENT; NAUSEA; NAUSEA AND VOMITING; NONHUMAN; PANCREAS CANCER; PANCREAS TUMOR; RASH; REVIEW; SIDE EFFECT; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION; UNSPECIFIED SIDE EFFECT; VOMITING; YERSINIA;

YERSINIA;

EID: 79953867228     PISSN: 15734080     EISSN: None     Source Type: Journal    
DOI: 10.2174/157340810793384124     Document Type: Review

References (103)

1. Ray, L.B.; Sturgill, T.W. Rapid stimulation by insulin of a serine/threonine kinase in 3T3-L1 adipocytes that phosphorylates microtubule-associated protein 2 in vitro. Proc. Natl. Acad. Sci. USA, 1987, 84, 1502-1506.
2. Ray, L.B.; Sturgill, T.W. Characterization of insulin-stimulated microtubule-associated protein kinase. Rapid isolation and stabilization of a novel serine/threonine kinase from 3T3-L1 cells. J. Biol. Chem., 1988, 263, 12721-12727.
3. Sturgill, T.W.; Ray, L.B. Muscle proteins related to microtubule associated protein-2 are substrates for an insulin-stimulatable kinase. Biochem. Biophys. Res. Commun., 1986, 134, 565-571.
4. Erickson, A.K.; Ray, L.B.; Sturgill, T.W. Microtubule-associated protein 1A is the fibroblast HMW MAP undergoing mitogenstimulated serine phosphorylation. Biochem. Biophys. Res. Commun., 1990, 166, 827-832.
5. Rossomando, A.J.; Payne, D.M.; Weber, M.J.; Sturgill, T.W. Evidence that pp42, a major tyrosine kinase target protein, is a mitogen-activated serine/threonine protein kinase. Proc. Natl. Acad. Sci. USA, 1989, 86, 6940-6943.
6. Boulton, T.G.; Yancopoulos, G.D.; Gregory, J.S.; Slaughter, C.; Moomaw, C.; Hsu, J.; Cobb, M.H. An insulin-stimulated protein kinase similar to yeast kinases involved in cell cycle control. Science, 1990, 249, 64-67.
7. Sato, C.; Nishizawa, K.; Nakayama, T.; Kobayashi, T. Effect upon mitogenic stimulation of calcium-dependent phosphorylation of cytoskeleton-associated 350,000and 80,000-mol-wt polypeptides in quiescent 3Y1 cells. J. Cell Biol., 1985, 100, 748-753.
8. Sato, C.; Nishizawa, K.; Nakayama, T.; Nose, K.; Takasaki, Y.; Hirose, S.; Nakamura, H. Intranuclear appearance of the phosphorylated form of cytoskeleton-associated 350-kDa proteins in U1-ribonucleoprotein regions after growth stimulation of fibroblasts. Proc. Natl. Acad. Sci. USA, 1986, 83, 7287-7291.
9. Ray, L.B.; Sturgill, T.W. Insulin-stimulated microtubule-associated protein kinase is phosphorylated on tyrosine and threonine in vivo. Proc. Natl. Acad. Sci. USA, 1988, 85, 3753-3757.
10. Anderson, N.G.; Maller, J.L.; Tonks, N.K.; Sturgill, T.W. Requirement for integration of signals from two distinct phosphorylation pathways for activation of MAP kinase. Nature, 1990, 343, 651-653.
11. Ahn, N.G.; Seger, R.; Bratlien, R.L.; Diltz, C.D.; Tonks, N.K.; Krebs, E.G. Multiple components in an epidermal growth factorstimulated protein kinase cascade. In vitro activation of a myelin basic protein/microtubule-associated protein 2 kinase. J. Biol. Chem., 1991, 266, 4220-4227.
12. Seger, R.; Ahn, N.G.; Posada, J.; Munar, E.S.; Jensen, A.M.; Cooper, J.A.; Cobb, M.H.; Krebs, E.G. Purification and characterization of mitogen-activated protein kinase activator(s) from epidermal growth factor-stimulated A431 cells. J. Biol. Chem., 1992, 267, 14373-14381.
13. Gomez, N.; Cohen, P. Dissection of the protein kinase cascade by which nerve growth factor activates MAP kinases. Nature, 1991, 353, 170-173.
14. Nakielny, S.; Cohen, P.; Wu, J.; Sturgill, T. MAP kinase activator from insulin-stimulated skeletal muscle is a protein threonine/tyrosine kinase. EMBO J., 1992, 11, 2123-2129.
15. Crews, C.M.; Erikson, R.L. Purification of a murine proteintyrosine/threonine kinase that phosphorylates and activates the Erk1 gene product: relationship to the fission yeast byr1 gene product. Proc. Natl. Acad. Sci. USA, 1992, 89, 8205-8209.
16. Rapp, U.R.; Goldsborough, M.D.; Mark, G.E.; Bonner, T.I.; Groffen, J.; Reynolds, F.H., Jr.; Stephenson, J.R. Structure and biological activity of v-raf, a unique oncogene transduced by a retrovirus. Proc. Natl. Acad. Sci. USA, 1983, 80, 4218-4222.
17. Kyriakis, J.M.; App, H.; Zhang, X.F.; Banerjee, P.; Brautigan, D.L.; Rapp, U.R.; Avruch, J. Raf-1 activates MAP kinase-kinase. Nature, 1992, 358, 417-421.
18. Dent, P.; Haser, W.; Haystead, T.A.; Vincent, L.A.; Roberts, T.M.; Sturgill, T.W. Activation of mitogen-activated protein kinase kinase by v-Raf in NIH 3T3 cells and in vitro. Science, 1992, 257, 1404-1407.
19. Sagata, N.; Oskarsson, M.; Copeland, T.; Brumbaugh, J.; Vande Woude, G.F. Function of c-mos proto-oncogene product in meiotic maturation in Xenopus oocytes. Nature, 1988, 335, 519-525.
20. English, J.; Pearson, G.; Wilsbacher, J.; Swantek, J.; Karandikar, M.; Xu, S.; Cobb, M.H. New insights into the control of MAP kinase pathways. Exp. Cell Res., 1999, 253, 255-270.
21. Pearson, G.; Robinson, F.; Beers Gibson, T.; Xu, B.E.; Karandikar, M.; Berman, K.; Cobb, M.H. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr. Rev., 2001, 22, 153-183.
22. Chen, Z.; Gibson, T.B.; Robinson, F.; Silvestro, L.; Pearson, G.; Xu, B.-E.; Wright, A.; Vanderbilt, C.; Cobb, M.H. MAP kinases. Chem. Rev., 2001, 101, 2449-2476.
23. Johnson, G.L.; Lapadat, R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science, 2002, 298, 1911-1912.
24. Roux, P.P.; Blenis, J. ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol. Mol. Biol. Rev., 2004, 68, 320-344.
25. Zheng, C.F.; Guan, K.L. Activation of MEK family kinases requires phosphorylation of two conserved Ser/Thr residues. EMBO J., 1994, 13, 1123-1131.
26. Alessi, D.R.; Saito, Y.; Campbell, D.G.; Cohen, P.; Sithanandam, G.; Rapp, U.; Ashworth, A.; Marshall, C.J.; Cowley, S. Identification of the sites in MAP kinase kinase-1 phosphorylated by p74raf-1. EMBO J., 1994, 13, 1610-1619.
27. Payne, D.M.; Rossomando, A.J.; Martino, P.; Erickson, A.K.; Her, J.H.; Shabanowitz, J.; Hunt, D.F.; Weber, M.J.; Sturgill, T.W. Identification of the regulatory phosphorylation sites in pp42/mitogen-activated protein kinase (MAP kinase). EMBO J., 1991, 10, 885-892.
28. Huang, C.Y.; Ferrell, J.E. Jr. Ultrasensitivity in the mitogenactivated protein kinase cascade. Proc. Natl. Acad. Sci. USA, 1996, 93, 10078-10083.
29. Mansour, S.J.; Matten, W.T.; Hermann, A.S.; Candia, J.M.; Rong, S.; Fukasawa, K.; Vande Woude, G.F.; Ahn, N.G. Transformation of mammalian cells by constitutively active MAP kinase kinase. Science, 1994, 265, 966-970.
30. Davies, H.; Bignell, G.R.; Cox, C.; Stephens, P.; Edkins, S.; Clegg, S.; Teague, J.; Woffendin, H.; Garnett, M.J.; Bottomley, W.; Davis, N.; Dicks, E.; Ewing, R.; Floyd, Y.; Gray, K.; Hall, S.; Hawes, R.; Hughes, J.; Kosmidou, V.; Menzies, A.; Mould, C.; Parker, A.; Stevens, C.; Watt, S.; Hooper, S.; Wilson, R.; Jayatilake, H.; Gusterson, B.A.; Cooper, C.; Shipley, J.; Hargrave, D.; PritchardJones, K.; Maitland, N.; Chenevix-Trench, G.; Riggins, G.J.; Bigner, D.D.; Palmieri, G.; Cossu, A.; Flanagan, A.; Nicholson, A.; Ho, J.W.C.; Leung, S.Y.; Yuen, S.T.; Weber, B.L.; Seigler, H.F.; Darrow, T.L.; Paterson, H.; Marais, R.; Marshall, C.J.; Wooster, R.; Stratton, M.R.; Futreal, P.A. Mutations of the BRAF gene in human cancer. Nature, 2002, 417, 949-954.
31. Kohno, M.; Pouyssegur, J. Pharmacological inhibitors of the ERK signaling pathway: application as anticancer drugs. Prog. Cell Cycle Res., 2003, 5, 219-224.
32. Sebolt-Leopold, J.S.; Herrera, R. Targeting the mitogen-activated protein kinase cascade to treat cancer. Nat. Rev. Cancer, 2004, 4, 937-947.
33. Kohno, M.; Pouyssegur, J. Targeting the ERK signaling pathway in cancer therapy. Ann. Med., 2006, 38, 200-211.
34. Hatzivassiliou, G.; Song, K.; Yen, I.; Brandhuber, B.J.; Anderson, D.J.; Alvarado, R.; Ludlam, M.J.; Stokoe, D.; Gloor, S.L.; Vigers, G.; Morales, T.; Aliagas, I.; Liu, B.; Sideris, S.; Hoeflich, K.P.; Jaiswal, B.S.; Seshagiri, S.; Koeppen, H.; Belvin, M.; Friedman, L.S.; Malek, S. RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth. Nature, 2010, 464, 431-435.
35. Heidorn, S.J.; Milagre, C.; Whittaker, S.; Nourry, A.; NiculescuDuvas, I.; Dhomen, N.; Hussain, J.; Reis-Filho, J.S.; Springer, C.J.; Pritchard, C.; Marais, R. Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF. Cell, 2010, 140, 209-221.
36. Poulikakos, P.I.; Zhang, C.; Bollag, G.; Shokat, K.M.; Rosen, N. RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF. Nature, 2010, 464, 427-430.
37. Dudley, D.T.; Pang, L.; Decker, S.J.; Bridges, A.J.; Saltiel, A.R. A synthetic inhibitor of the mitogen-activated protein kinase cascade. Proc. Natl. Acad. Sci. USA, 1995, 92, 7686-7689.
38. Alessi, D.R.; Cuenda, A.; Cohen, P.; Dudley, D.T.; Saltiel, A.R. PD 098059 is a specific inhibitor of the activation of mitogenactivated protein kinase kinase in vitro and in vivo. J. Biol. Chem., 1995, 270, 27489-27494.
39. Davies, S.P.; Reddy, H.; Caivano, M.; Cohen, P. Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem. J., 2000, 351, 95-105.
40. Kamakura, S.; Moriguchi, T.; Nishida, E. Activation of the protein kinase ERK5/BMK1 by receptor tyrosine kinases. identification and characterization of a signaling pathway to the nucleus. J. Biol. Chem., 1999, 274, 26563-26571.
41. Mody, N.; Leitch, J.; Armstrong, C.; Dixon, J.; Cohen, P. Effects of MAP kinase cascade inhibitors on the MKK5/ERK5 pathway. FEBS Lett., 2001, 502, 21-24.
42. Ahn, N.G.; Stines Nahreini, T.; Tolwinski, N.S.; Resing, K.A.; Balch, W.E. Pharmacologic Inhibitors of MKK1 and MKK2. In: Methods in Enzymology, Academic Press: 2001; Vol. 332, pp 417-431.
43. Favata, M.F.; Horiuchi, K.Y.; Manos, E.J.; Daulerio, A.J.; Stradley, D.A.; Feeser, W.S.; Van Dyk, D.E.; Pitts, W.J.; Earl, R.A.; Hobbs, F.; Copeland, R.A.; Magolda, R.L.; Scherle, P.A.; Trzaskos, J.M. Identification of a novel inhibitor of mitogen-activated protein kinase kinase. J. Biol. Chem., 1998, 273, 18623-18632.
44. Sebolt-Leopold, J.S.; Dudley, D.T.; Herrera, R.; Becelaere, K.V.; Wiland, A.; Gowan, R.C.; Tecle, H.; Barrett, S.D.; Bridges, A.; Przybranowski, S.; Leopold, W.R.; Saltiel, A.R. Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo. Nat. Med., 1999, 5, 810-816.
45. Solit, D.B.; Garraway, L.A.; Pratilas, C.A.; Sawai, A.; Getz, G.; Basso, A.; Ye, Q.; Lobo, J.M.; She, Y.; Osman, I.; Golub, T.R.; Sebolt-Leopold, J.; Sellers, W.R.; Rosen, N. BRAF mutation predicts sensitivity to MEK inhibition. Nature, 2006, 439, 358.
46. LoRusso, P.M.; Adjei, A.A.; Varterasian, M.; Gadgeel, S.; Reid, J.; Mitchell, D.Y.; Hanson, L.; DeLuca, P.; Bruzek, L.; Piens, J.; Asbury, P.; Van Becelaere, K.; Herrera, R.; Sebolt-Leopold, J.; Meyer, M.B. Phase I and pharmacodynamic study of the oral mek inhibitor CI-1040 in patients with advanced malignancies. J. Clin. Oncol., 2005, 23, 5281-5293.
47. Allen, L.F.; Sebolt-Leopold, J.; Meyer, M.B. CI-1040 (PD184352), a targeted signal transduction inhibitor of MEK (MAPKK). Semin. Oncol., 2003, 30(Supplement 16), 105-116.
48. Rinehart, J.; Adjei, A.A.; LoRusso, P.M.; Waterhouse, D.; Hecht, J.R.; Natale, R.B.; Hamid, O.; Varterasian, M.; Asbury, P.; Kaldjian, E.P.; Gulyas, S.; Mitchell, D.Y.; Herrera, R.; SeboltLeopold, J.S.; Meyer, M.B. Multicenter phase II study of the oral mek inhibitor, CI-1040, in patients with advanced non-small-cell lung, breast, colon, and pancreatic cancer. J. Clin. Oncol., 2004, 22, 4456-4462.
49. Sebolt-Leopold, J.S.; Merriman, R.; Omer, C.; Tecle, H.; Bridges, A.; Klohs, W.; Loi, C.-M.; Valik, H.; Przybranowski, S.; Meyer, M.; Leopold, W.R. In: The biological profile of PD 0325901: A second generation analog of CI-1040 with improved pharmaceutical potential, Annual Meeting of the American Association for Cancer Research, March 1, 2004; 2004; p 925.
50. Dankort, D.; Filenova, E.; Collado, M.; Serrano, M.; Jones, K.; McMahon, M. A new mouse model to explore the initiation, progression, and therapy of BRAFV600E-induced lung tumors. Genes Devel., 2007, 21, 379-384.
51. Dankort, D.; Curley, D.P.; Cartlidge, R.A.; Nelson, B.; Karnezis, A.N.; Damsky W.E. Jr; You, M.J.; DePinho, R.A.; McMahon, M.; Bosenberg, M. BrafV600E cooperates with Pten loss to induce metastatic melanoma. Nat. Genet., 2009, 41, 544-552.
52. Lorusso, P.; Krishnamurthi, S.; Rinehart, J.R.; Nabell, L.; Croghan, G.; Varterasian M.; Sadis, S.S.; Menon, S.S.; Leopold, J.; Meyer, M.B. In: A phase 1-2 clinical study of a second generation oral MEK inhibitor, PD 0325901 in patients with advanced cancer, American Society of Clinical Oncology Annual Meeting, June 1, 2005; 2005; p 3011.
53. Menon, S.S.; Whitfield, L.R.; Sadis, S.; Meyer, M.B.; Leopold, J.; Lorusso, P.M.; Krishnamurthi, S.; Rinehart, J.R.; Nabell, L.; Croghan, G. In: Pharmacokinetics (PK) and pharmacodynamics (PD) of PD 0325901, a second generation MEK inhibitor after multiple oral doses of PD 0325901 to advanced cancer patients, American Society of Clinical Oncology Annual Meeting, June 1, 2005; 2005; p 3066.
54. U.S. National Institutes of Health. A service of the U.S. National Institutes of Health: Clinical Trials. gov Identifier: NCT00147550. MEK Inhibitor PD-325901 To Treat Advanced Breast Cancer, Colon Cancer, And Melanoma. http://clinicaltrials.gov/ct2/show/ NCT00147550 (Accessed August 12, 2009)
55. Warmus, J.S.; Flamme, C.; Zhang, L.Y.; Barrett, S.; Bridges, A.; Chen, H.; Gowan, R.; Kaufman, M.; Sebolt-Leopold, J.; Leopold, W.; Merriman, R.; Ohren, J.; Pavlovsky, A.; Przybranowski, S.; Tecle, H.; Valik, H.; Whitehead, C.; Zhang, E. 2-Alkylaminoand alkoxy-substituted 2-amino-1,3,4-oxadiazoles--O-Alkyl benzohydroxamate esters replacements retain the desired inhibition and selectivity against MEK (MAP ERK kinase). Bioorg. Med. Chem. Lett., 2008, 18, 6171-6174.
56. Wallace, E.; Yeh, T.; Lyssikatos, J.; Winkler, J.; Lee, P.; Marlow, A.; Hurley, B.; Marsh, V.; Bernat, B.; Evans, R.; Colwell, H.; Ballard, J.; Morales, T.; Smith, D.; Brandhuber, B.; Gross, S.; Poch, G.; Litwiler, K.; Hingorani, G.; Otten, J.; Sullivan, F.; Blake, J.; Pheneger, T.; Goyette, M.; Koch, K. In: Preclinical development of ARRY-142886, a potent and selective MEK inhibitor, Annual Meeting of the American Association for Cancer Research, March 1, 2004; 2004; pp 897-a.
57. Lyssikatos, J.; Yeh, T.; Wallace, E.; Marsh, V.; Bernat, B.; Gross, S.; Evans, R.; Colwell, H.; Parry, J.; Baker, S.; Ballard, J.; Morales, T.; Smith, D.; Brandhuber, B.; Winkler, J. In: ARRY-142886, a potent and selective MEK inhibitor: I) ATP-independent inhibition results in high enzymatic and cellular selectivity, Annual Meeting of the American Association for Cancer Research, March 1, 2004; 2004; pp 896-b.
58. Yeh, T.C.; Marsh, V.; Bernat, B.A.; Ballard, J.; Colwell, H.; Evans, R.J.; Parry, J.; Smith, D.; Brandhuber, B.J.; Gross, S.; Marlow, A.; Hurley, B.; Lyssikatos, J.; Lee, P.A.; Winkler, J.D.; Koch, K.; Wallace, E. Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor. Clin. Cancer Res., 2007, 13, 1576-1583.
59. Yeh, T.; Wallace, E.; Lyssikatos, J.; Winkler, J. In: ARRY-142886, a potent and selective MEK inhibitor: II) Potency against cellular MEK leads to inhibition of cellular proliferation and induction of apoptosis in cell lines with mutant Ras or B-Raf, Annual Meeting of the American Association for Cancer Research, March 1, 2004; 2004; pp 896-c-897.
60. Haass, N.K.; Sproesser, K.; Nguyen, T.K.; Contractor, R.; Medina, C.A.; Nathanson, K.L.; Herlyn, M.; Smalley, K.S.M. The mitogenactivated protein/extracellular signal-regulated kinase kinase inhibitor AZD6244 (ARRY-142886) induces growth arrest in melanoma cells and tumor regression when combined with docetaxel. Clin. Cancer Res., 2008, 14, 230-239.
61. Lee, P.; Wallace, E.; Yeh, T.; Poch, G.; Litwiler, K.; Pheneger, T.; Lyssikatos, J.; Winkler, J. In: ARRY-142886, a potent and selective MEK inhibitor: III) Efficacy in murine xenograft models correlates with decreased ERK phosphorylation, Annual Meeting of the American Association for Cancer Research, March 1, 2004; 2004; p 897.
62. Adjei, A.A.; Cohen, R.B.; Franklin, W.; Morris, C.; Wilson, D.; Molina, J.R.; Hanson, L.J.; Gore, L.; Chow, L.; Leong, S.; Maloney, L.; Gordon, G.; Simmons, H.; Marlow, A.; Litwiler, K.; Brown, S.; Poch, G.; Kane, K.; Haney, J.; Eckhardt, S.G. Phase I pharmacokinetic and pharmacodynamic study of the oral, smallmolecule mitogen-activated protein kinase kinase 1/2 inhibitor AZD6244 (ARRY-142886) in patients with advanced cancers. J. Clin. Oncol., 2008, 26, 2139-2146.
63. Ohren, J.F.; Chen, H.; Pavlovsky, A.; Whitehead, C.; Zhang, E.; Kuffa, P.; Yan, C.; McConnell, P.; Spessard, C.; Banotai, C.; Mueller, W.T.; Delaney, A.; Omer, C.; Sebolt-Leopold, J.; Dudley, D.T.; Leung, I.K.; Flamme, C.; Warmus, J.; Kaufman, M.; Barrett, S.; Tecle, H.; Hasemann, C.A. Structures of human MAP kinase kinase 1 (MEK1) and MEK2 describe novel noncompetitive kinase inhibition. Nat. Struct. Mol. Biol., 2004, 11, 1192-1197.
64. Fischmann, T.O.; Smith, C.K.; Mayhood, T.W.; Myers, J.E.; Reichert, P.; Mannarino, A.; Carr, D.; Zhu, H.; Wong, J.; Yang, R.S.; Le, H.V.; Madison, V.S. Crystal structures of MEK1 binary and ternary complexes with nucleotides and nhibitors. Biochemistry, 2009, 48, 2661-2674.
65. Duesbery, N.S.; Webb, C.P.; Leppla, S.H.; Gordon, V.M.; Klimpel, K.R.; Copeland, T.D.; Ahn, N.G.; Oskarsson, M.K.; Fukasawa, K.; Paull, K.D.; Vande Woude, G.F. Proteolytic inactivation of MAPkinase-kinase by anthrax lethal factor. Science, 1998, 280, 734-737.
66. Vitale, G.; Pellizzari, R.; Recchi, C.; Napolitani, G.; Mock, M.; Montecucco, C. Anthrax lethal factor cleaves the N-terminus of MAPKKs and induces tyrosine/threonine phosphorylation of MAPKs in cultured macrophages. Biochem. Biophys. Res. Commun., 1998, 248, 706-711.
67. Singh, Y.; Liang, X.; Duesbery, N.S. Pathogenesis of Bacillus anthracis: the role of anthrax toxins. In: Microbial Toxins Molecular and Cellular Biology, Proft, T., Ed. Horizon Bioscience: Norfolk, England, 2005; pp 285-312.
68. Pellizzari, R.; Guidi-Rontani, C.; Vitale, G.; Mock, M.; Montecucco, C. Anthrax lethal factor cleaves MKK3 in macrophages and inhibits the LPS/IFNgamma-induced release of NO and TNFalpha. FEBS Lett., 1999, 462, 199-204.
69. Vitale, G.; Bernardi, L.; Napolitani, G.; Mock, M.; Montecucco, C. Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor. Biochem. J., 2000, 352, 739-745.
70. Duesbery, N.S.; Resau, J.; Webb, C.P.; Koochekpour, S.; Koo, H.M.; Leppla, S.H.; Vande Woude, G.F. Suppression of rasmediated transformation and inhibition of tumor growth and angiogenesis by anthrax lethal factor, a proteolytic inhibitor of multiple MEK pathways. Proc. Natl. Acad. Sci. USA, 2001, 98, 4089-4094.
71. Tanoue, T.; Adachi, M.; Moriguchi, T.; Nishida, E. A conserved docking motif in MAP kinases common to substrates, activators and regulators. Nat. Cell Biol., 2000, 2, 110-116.
72. Chopra, A.P.; Boone, S.A.; Liang, X.; Duesbery, N.S. Anthrax lethal factor proteolysis and inactivation of MAPK kinase. J. Biol. Chem., 2003, 278, 9402-9406.
73. Bardwell, A.J.; Abdollahi, M.; Bardwell, L. Anthrax lethal factorcleavage products of MAPK (mitogen-activated protein kinase) kinases exhibit reduced binding to their cognate MAPKs. Biochem. J., 2004, 378, 569-577.
74. Friedlander, A.M. In: Antitumor effects of anthrax lethal toxin, Third International Conference on Anthrax, University of Plymouth, September 7-10, 1998; University of Plymouth, 1998; p 104.
75. Koo, H.-M.; VanBrocklin, M.; McWilliams, M.J.; Leppla, S.H.; Duesbery, N.S.; Woude, G.F.V. Apoptosis and melanogenesis in human melanoma cells induced by anthrax lethal factor inactivation of mitogen-activated protein kinase kinase. Proc. Natl. Acad. Sci. USA, 2002, 99, 3052-3057.
76. Abi-Habib, R.J.; Urieto, J.O.; Liu, S.; Leppla, S.H.; Duesbery, N.S.; Frankel, A.E. BRAF status and mitogen-activated protein/extracellular signal-regulated kinase kinase 1/2 activity indicate sensitivity of melanoma cells to anthrax lethal toxin. Mol. Cancer Ther., 2005, 4, 1303-1310.
77. Depeille, P.; Young, J.J.; Boguslawski, E.A.; Berghuis, B.D.; Kort, E.J.; Resau, J.H.; Frankel, A.E.; Duesbery, N.S. Anthrax lethal toxin inhibits growth of and vascular endothelial growth factor release from endothelial cells expressing the human herpes virus 8 viral G protein coupled receptor. Clin. Cancer Res., 2007, 13, 5926-5934.
78. Ding, Y.; Boguslawski, E.A.; Berghuis, B.D.; Young, J.J.; Zhang, Z.; Hardy, K.; Furge, K.; Kort, E.; Frankel, A.E.; Hay, R.V.; Resau, J.H.; Duesbery, N.S. Mitogen-activated protein kinase kinase signaling promotes growth and vascularization of fibrosarcoma. Mol. Cancer Ther., 2008, 7, 648-658.
79. Huang, D.; Ding, Y.; Luo, W.-M.; Bender, S.; Qian, C.-N.; Kort, E.; Zhang, Z.-F.; VandenBeldt, K.; Duesbery, N.S.; Resau, J.H.; Teh, B.T. Inhibition of MAPK kinase signaling pathways suppressed renal cell carcinoma growth and angiogenesis in vivo. Cancer Res., 2008, 68, 81-88.
80. Rouleau, C.; Menon, K.; Boutin, P.; Guyre, C.; Yoshida, H.; Kataoka, S.; Perricone, M.; Shankara, S.; Frankel, A.E.; Duesbery, N.S.; Vande Woude, G.; Biemann, H.P.; Teicher, B.A. The systemic administration of lethal toxin achieves a growth delay of human melanoma and neuroblastoma xenografts: assessment of receptor contribution. Int. J. Oncol., 2008, 32, 739-748.
81. Abi-Habib, R.J.; Singh, R.; Leppla, S.H.; Greene, J.J.; Ding, Y.; Berghuis, B.; Duesbery, N.S.; Frankel, A.E. Systemic anthrax lethal toxin therapy produces regressions of subcutaneous human melanoma tumors in athymic nude mice. Clin. Cancer Res., 2006, 12, 7437-7443.
82. Abi-Habib, R.J.; Singh, R.; Liu, S.; Bugge, T.H.; Leppla, S.H.; Frankel, A.E. A urokinase-activated recombinant anthrax toxin is selectively cytotoxic to many human tumor cell types. Mol. Cancer Ther., 2006, 5, 2556-2562.
83. Liu, S.; Wang, H.; Currie, B.M.; Molinolo, A.; Leung, H.J.; Moayeri, M.; Basile, J.R.; Alfano, R.W.; Gutkind, J.S.; Frankel, A.E.; Bugge, T.H.; Leppla, S.H. Matrix metalloproteinase-activated anthrax lethal toxin demonstrates high potency in targeting tumor vasculature. J. Biol. Chem., 2008, 283, 529-540.
84. Liu, S.; Wang, H.; Currie, B.M.; Molinolo, A.; Leung, H.J.; Moayeri, M.; Basile, J.R.; Alfano, R.W.; Gutkind, J.S.; Frankel, A.E.; Bugge, T.H.; Leppla, S.H. Matrix metalloproteinase-activated anthrax lethal toxin demonstrates high potency in targeting tumor vasculature. J. Biol. Chem., 2008, 283, 529-540.
85. Kirby, J.E. Anthrax lethal toxin induces human endothelial cell apoptosis. Infect. Immun., 2004, 72, 430-439.
86. Warfel, J.M.; Steele, A.D.; D'Agnillo, F. Anthrax lethal toxin induces endothelial barrier dysfunction. Am. J. Pathol., 2005, 166, 1871-1881.
87. Alfano, R.W.; Leppla, S.H.; Liu, S.; Bugge, T.H.; Meininger, C.J.; Lairmore, T.C.; Mulne, A.F.; Davis, S.H.; Duesbery, N.S.; Frankel, A.E. Matrix metalloproteinase-activated anthrax lethal toxin inhibits endothelial invasion and neovasculature formation during in vitro morphogenesis. Mol. Cancer Res., 2009, 7, 452-461.
88. Mavria, G.; Vercoulen, Y.; Yeo, M.; Paterson, H.; Karasarides, M.; Marais, R.; Bird, D.; Marshall, C.J. ERK-MAPK signaling opposes Rho-kinase to promote endothelial cell survival and sprouting during angiogenesis. Cancer Cell, 2006, 9, 33-44.
89. Park, J.M.; Greten, F.R.; Li, Z.-W.; Karin, M. Macrophage apoptosis by anthrax lethal factor through p38 MAP kinase inhibition. Science, 2002, 297, 2048-2051.
90. Agrawal, A.; Lingappa, J.; Leppla, S.H.; Agrawal, S.; Jabbar, A.; Quinn, C.; Pulendran, B. Impairment of dendritic cells and adaptive immunity by anthrax lethal toxin. Nature, 2003, 424, 329-334.
91. Bromberg-White, J.L.; Boguslawski, E.; Duesbery, N.S. Perturbation of mouse retinal vascular morphogenesis by anthrax lethal toxin. PLoS One, 2009, 4, e6956.
92. Palmer, L.E.; Hobbie, S.; Galan, J.E.; Bliska, J.B. YopJ of Yersinia pseudotuberculosis is required for the inhibition of macrophage TNF-alpha production and downregulation of the MAP kinases p38 and JNK. Mol. Microbiol., 1998, 27, 953-965.
93. Palmer, L.E.; Pancetti, A.R.; Greenberg, S.; Bliska, J.B. YopJ of Yersinia spp. is sufficient to cause downregulation of multiple mitogen-activated protein kinases in eukaryotic cells. Infect. Immun., 1999, 67, 708-716.
94. Schesser, K.; Spiik, A.-K.; Dukuzumuremyi, J.-M.; Neurath, M.F.; Pettersson, S.; Wolf-Watz, H. The yopJ locus is required for Yersinia-mediated inhibition of NF-kappaB activation and cytokine expression: YopJ contains a eukaryotic SH2-like domain that is essential for its repressive activity. Mol. Microbiol., 1998, 28, 1067-1079.
95. Ruckdeschel, K.; Harb, S.; Roggenkamp, A.; Hornef, M.; Zumbihl, R.; Kohler, S.; Heesemann, J.; Rouot, B. Yersinia enterocolitica impairs activation of transcription factor NF-kappa B: involvement in the induction of programmed cell death and in the suppression of the macrophage tumor necrosis factor alpha production. J. Exp. Med., 1998, 187, 1069-1079.
96. Orth, K.; Palmer, L.E.; Bao, Z.Q.; Stewart, S.; Rudolph, A.E.; Bliska, J.B.; Dixon, J.E. Inhibition of the mitogen-activated protein kinase kinase superfamily by a yersinia effector. Science, 1999, 285, 1920-1923.
97. Orth, K.; Xu, Z.; Mudgett, M.B.; Bao, Z.Q.; Palmer, L.E.; Bliska, J.B.; Mangel, W.F.; Staskawicz, B.; Dixon, J.E. Disruption of signaling by yersinia effector YopJ, a ubiquitin-like protein protease. Science, 2000, 290, 1594-1597.
98. Mittal, R.; Peak-Chew, S.-Y.; McMahon, H.T. Acetylation of MEK2 and IκB kinase (IKK) activation loop residues by YopJ inhibits signaling. Proc. Natl. Acad. Sci. USA, 2006, 103, 18574-18579.
99. Mukherjee, S.; Keitany, G.; Li, Y.; Wang, Y.; Ball, H.L.; Goldsmith, E.J.; Orth, K. Yersinia YopJ acetylates and inhibits kinase activation by blocking phosphorylation. Science, 2006, 312, 1211-1214.
100. Hao, Y.-H.; Wang, Y.; Burdette, D.; Mukherjee, S.; Keitany, G.; Goldsmith, E.; Orth, K. Structural requirements for Yersinia YopJ inhibition of MAP kinase pathways. PLoS One, 2008, 3, e1375.
101. Ghosh, P. Process of protein transport by the type III secretion system. Microbiol. Mol. Biol. Rev., 2004, 68, 771-795.
102. Chong, H.; Vikis, H.G.; Guan, K.L. Mechanisms of regulating the Raf kinase family. Cell Signal., 2003, 15, 463-469.
103. Friday, B.B.; Yu, C.; Dy, G.K.; Smith, P.D.; Wang, L.; Thibodeau, S.N.; Adjei, A.A. BRAF V600E disrupts AZD6244-induced abrogation of negative feedback pathways between extracellular signal-regulated kinase and Raf proteins. Cancer Res., 2008, 68, 6145-6153.