Tyrosine kinases as new molecular targets in treatment of inflammatory disorders and leukemia

Current Pharmaceutical Design

Volumn 10, Issue 10, 2004, Pages 1083-1091

  Uckun, Fatih M ^a   Mao, Chen ^a  

^a PARKER HUGHES INSTITUTE   (United States)

Author keywords

BTK; Computational chemistry; Inflammation; JAK3; Leukemia; PTK; SAR; Structure based drug design

Indexed keywords

2,6 DIAMINO 4 CYCLOHEXYLMETHOXY 5 NITROSOPYRIMIDINE; 2,6 DIAMINO 4 CYCLOHEXYLMETHYLOXY 5 NITROSOPYRIMIDINE; 3 [4 METHYL 2 (2 OXO 3 INDOLINYLMETHYLIDENYL) 3 PYRROLYL]PROPIONIC ACID; 4 (4 FLUOROPHENYL) 2 (4 METHYLSULFINYLPHENYL) 5 (4 PYRIDYL)IMIDAZOLE; 4 (4 HYDROXYANILINO) 6,7 DIMETHOXYQUINAZOLINE; 6 O CYCLOHEXYLMETHYLGUANINE; ACETYLSALICYLIC ACID; ALPHA CYANO BETA HYDROXY BETA METHYL N (2,5 DIBROMOPHENYL)PROPENAMIDE; BRUTON TYROSINE KINASE; CERAMIDE; ENZYME INHIBITOR; IMATINIB; IMIDAZOLE DERIVATIVE; INDIRUBIN; ISOQUINOLINE DERIVATIVE; JANUS KINASE; LFM A13; N BENZYL 2 CYANO 3 (3,4 DIHYDROXYPHENYL)ACRYLAMIDE; OXINDOLE; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE KINASE INHIBITOR; PURINE DERIVATIVE; PURVALANOL; PURVALANOL B; QUINAZOLINE DERIVATIVE; SB 216995; STAUROSPORINE; SU 4984; TACROLIMUS; TYRPHOSTIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; VINCRISTINE;

CELLULAR DISTRIBUTION; DOSE RESPONSE; DRUG DESIGN; DRUG EFFICACY; DRUG RECEPTOR BINDING; DRUG STRUCTURE; DRUG TARGETING; GRAFT VERSUS HOST REACTION; HUMAN; HUMAN CELL; INFLAMMATORY DISEASE; LEUKEMIA; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN LOCALIZATION; PROTEIN STRUCTURE; PROTEIN TARGETING; REVIEW; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

ANIMALS; ANTI-INFLAMMATORY AGENTS; ANTINEOPLASTIC AGENTS; DRUG DESIGN; ENZYME INHIBITORS; HUMANS; INFLAMMATION; LEUKEMIA; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PROTEIN-TYROSINE KINASES;

EID: 1842431413     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/1381612043452677     Document Type: Review

References (59)

1. Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S. The protein kinase complement of the human genome. Science 2002; 298(5600): 1912-34.
2. Dunn D. Mining the human 'kinome'. Drug Discovery Today 2002; 7(22): 1121-1123.
3. Traxler P. Tyrosine kinases as targets in cancer therapy - successes and failures. 2003; 7(2): 215-34.
4. McTigue MA, Wickersham JA, Pinko C, Showalter RE, Parast CV, Tempczyk-Russell A, et al. Crystal structure of the kinase domain of human vascular endothelial growth factor receptor 2: A key enzyme in angiogenesis. Structure With Folding & Design 1999; 7(3): 319-30.
5. Modjtahedi H, Affleck K, Stubberfield C, Dean C. EGFR blockade by tyrosine kinase inhibitor or monoclonal antibody inhibits growth, directs terminal differentiation and induces apoptosis in the human squamous cell carcinoma HN5. Int J Oncol 1998; 13(2): 335-42.
6. Traxler P, Green J, Mett H, Sequin U, Furet P. Use of a pharmacophore model for the design of EGFR tyrosine kinase inhibitors: isoflavones and 3-phenyl-4(1H)-quinolones. Journal of Medicinal Chemistry 1999; 42(6): 1018-26.
7. Uckun FM, Sudbeck EA, Mao C, Ghosh S, Liu XP, Vassilev AO, et al. Structure-based design of novel anticancer agents. 2001; 1(1): 59-71.
8. Hubbard SR. Structural analysis of receptor tyrosine kinases. progress in biophysics and molecular biology 1999; 71(3-4): 343-58.
9. Xu W, Harrison SC, Eck MJ. Three-dimensional structure of the tyrosine kinase c-Src. Nature 1997; 385(6617): 595-602.
10. Xu W, Doshi A, Lei M, Eck MJ, Harrison SC. Crystal structures of c-Src reveal features of its autoinhibitory mechanism. Mol Cell 1999; 3(5): 629-38.
11. Sicheri F, Moarefi I, Kuriyan J. Crystal structure ofthe Src family tyrosine kinase Hck. Nature 1997; 385(6617): 602-9.
12. Schindler T, Sicheri F, Pico A, Gazit A, Levitzki A, Kuriyan J. Crystal structure of Hck in complex with a Src family-selective tyrosine kinase inhibitor. 1999; 3(5): 639-48.
13. Mao C, Zhou M, Uckun FM. Crystal structure of Bruton's tyrosine kinase domain suggests a novel pathway for activation and provides insights into the molecular basis of X-linked agammaglobulinemia. The Journal of Biological Chemistry 2001; 276(44): 41435-43.
14. Zhu X, Kim JL, Newcomb JR, Rose PE, Stover DR, Toledo LM, et al. Structural analysis of the lymphocyte-specific kinase Lck in complex with non-selective and Src family selective kinase inhibitors. 1999; 7(6): 651-61.
15. Yamaguchi H, Hendrickson WA. Structural basis for activation of human lymphocyte kinase Lck upon tyrosine phosphorylation. Nature 1996; 384(6608): 484-9.
16. Mohammadi M, Schlessinger J, Hubbard SR. Structure of the FGF receptor tyrosine kinase domain reveals a novel autoinhibitory mechanism. Cell 1996; 86(4): 577-87.
17. Mohammadi M, McMahon G, Sun L, Tang C, Hirth P, Yeh BK, et al. Structures of the tyrosme kinase domain of fibroblast growth factor receptor in complex with inhibitors. Science 1997; 276(5314): 955-60.
18. Schindler T, Bornmann W, Pellicena P, Miller WT, Clarkson B, Kuriyan J. Structural mechanism for STI-571 inhibition of abelson tyrosine kinase. Science 2000; 289(5486): 1938-42.
19. Munshi S, Kornienko M, Hall DL, Reid JC, Waxman L, Stirdivant SM, el al. Crystal structure of the Apo, unactivated insulin-like growth factor-1 receptor kinase. Implication for inhibitor specificity. The Journal of Biological Chemistry 2002; 277(41): 38797-802.
20. Cetkovic-Cvrlje M, Roers BA, Schonhoff D, Waurzyniak B, Liu XP, Uckun FM. Treatment of post-bone marrow transplant acute graft-versus-host disease with a rationally designed JAK3 inhibitor. Leukemia & Lymphoma 2002; 43(7): 1447-53.
21. Uckun FM, Roers BA, Waurzyniak B, Liu XP, Cetkovic-Cvrlje M. Janus kinase 3 inhibitor WHI-P131/JANEX-1 prevents graft-versus-host disease but spares the graft-versus-leukemia function of the bone marrow allografts in a murine bone marrow transplantation model. Blood 2002; 99(11): 4192-9.
22. Malaviya R, Uckun FM. Genetic and biochemical evidence for a critical role of Janus kinase (JAK)-3 in mast cell-mediated type I hypersensitivity reactions. Biochem Biophys Res Commun 1999; 257(3): 807-13.
23. Goodman PA, Niehoff LB, Uckun FM. Role of tyrosine kinases in induction of tile c-jun proto-oncogene in irradiated B-lineage lymphoid cells. J Biol Chem 1998; 273: 17742-48.
24. Sudbeck EA, Liu XP, Narla RK, Mahajan S, Ghosh S, Mao C, et al. Structure-based design of specific inhibitors of Janus kinase 3 as apoptosis-inducing antileukemic agents. Clinical Cancer Research: An Official Journal of the Am Associ Cancer Res 1999; 5(6): 1569-82.
25. Malavija R, Chen CL, Liu XP, Uckun FM. In vivo pharmacokinetics and anti-anaphylactic activity of the novel mast cell inhibitor 4-(4′-hydroxylphenyl)-amino-6,7-dimethoxyquinazoline (WHI-P131). Am J Therapeut 2001; 8(1): 35-9.
26. Sudbeck EA, Liu XP, Narla RK, Mahajan S, Ghosh S, Mao C, et al. Structure-based design of specific inhibitors of Janus kinase 3 as apoptosis-inducing antileukemic agents. Clin Cancer Res 1999; 5(6): 1569-82.
27. Tibbles HE, Vassilev A, Wendorf H, Schonhoff D, Zhu D, Lorenz D, et al. Role of a JAK3-dependent biochemical signaling pathway in platelet activation and aggregation. J Biol Chem 2001; 276(21): 17815-22.
28. Trieu VN, Lin R, Liu XP, Uckun FM. A specific inhibitor of Janus kinase-3 increases survival in a transgenic mouse model of amyotrophic lateral sclerosis. Biochem Biophys Res Commun 2000, 267(1): 22-5.
29. Kurosaki T. Molecular mechanisms in B-cell antigen receptor signaling. Curr Opin Immunol 1997; 9: 309-318.
30. Mahajan S, Ghosh S, Sudbeck EA, Zheng Y, Downs S, Hupke M, el al. Rational design and synthesis of a novel anti-leukemic agent targeting Bruton's tyrosine kinase (BTK), LFM-A13 [alpha-cyano-beta-hydroxy-beta-methyl-N-(2, 5-dibromophenyl)propenamide]. J Biol Chem 1999; 274(14): 9587-99.
31. Vassilev A, Ozer Z, Navara C, Mahajan S, Uckun FM. Bruton's tyrosine kinase as an inhibitor of the Fas/CD95 death-inducing signaling complex. J Biol Chem 1999; 274(3): 1646-56.
32. Rawlings DJ, Witte ON. Bruton's tyrosine kinase is a key regulator in B-cell development. Immunol Reviews 1994; 138: 105-19.
33. Uckun FM, Waddick KG, Mahajan S, Jun X, Takata M, Bolen J, et al. BTK as a mediator of radiation-induced apoptosis in DT-40 lymphoma B cells. Science 1996; 273(5278): 1096-100.
34. Kurosaki T, Tsukada S. BLNK: Connecting Syk and Btk to calcium signals. Immunity 2000, 12(1): 1-5.
35. Bence K, Ma W, Kozasa T, Huang XY. Direct stimulation of Bruton's tyrosine kinase by G(q)-protein alpha-subunit. Nature 1997; 389(6648): 296-9.
36. Mahajan S, Ghosh S, Sudbeck EA, Zheng Y, Downs S, Hupke M, et al. Rational design and synthesis of a novel anti-leukemic agent targeting Bruton's tyrosine kinase (BTK), LFM-A13 [alpha-cyano-beta-hydroxy-beta-methyl-N-(2, 5-dibromophenyl)propenamide]. J Biol Chem 1999; 274(14): 9587-99.
37. Davis ST, et al. Prevention of chemotherapy-induced alopecia in rats by CDK inhibitors. Science 2001; 291(5501): 134-7.
38. Mohammadi M, McMahon G, Sun L, Tang C, Hirth P, Yeh BK, et al. Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors. Science 1997; 276(5314): 955-60.
39. Wang Z, Canagarajah BJ, Boehm JC, Kassisa S, Cobb MH, Young PR, et al. Structural basis of inhibitor selectivity in MAP kinases. Structure 1998; 6(9): 1117-28.
40. Gray NS, Wodicka L, Thunnissen AM, Norman TC, Kwon S, Espinoza FH, et al. Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors. Science 1998; 281(5376): 533-8.
41. Xu RM, Carmel G, Kuret J, Cheng X. Structural basis for selectivity of the isoquinoline sulfonamide family of protein kinase inhibitors. Proc Natl Acad Sci USA 1996; 93(13: 6308-13): 6308-13.
42. Shewchuk L, Hassell A, Wisely B, Rocque W, Holmes W, Veal J, et al. Binding mode of the 4-anilinoquinazoline class of protein kinase inhibitor: X-ray crystallographic studies of 4-anilinoquinazolines bound to cyclin-dependent kinase 2 and p38 kinase. J Med Chem 2000; 43(1): 133-8.
43. Stamos J, Sliwkowski MX, Eigenbrot C. Structure of the Epidermal Growth Factor Receptor Kinase Domain Alone and in Complex with a 4-Anilinoquinazoline Inhibitor. J Biol Chem 2002; 277(48): 46265-72.
44. Davies T, Tunnah P, Meijer L, Marko D, Eisenbrand G, Endicott J, et al. Inhibitor Binding to Active and Inactive CDK2The Crystal Structure of CDK2-Cyclin A/Indirubin-5-Sulphonate. Structure 2001; 9(5): 389-397.
45. Toledo L, Lydon N. Structures of staurosporine bound to CDK2 and cAPK – new tools for structure-based design of protein kinase inhibitors. Structure 1997; 5(12): 1551-1556.
46. Lamers M, Antson A, Hubbard R, Scott R, Williams D. Structure of the Protein Tyrosine Kinase Domain of C-terminal Src Kinase (CSK) in Complex with Staurosporine. J Mol Biol 1999; 285(2): 713-725.
47. Arris CE, Boyle FT, Calvert AH, Curtin NJ, Endicott JA, Garman EF, et al. Identification of novel purine and pyrimidine cyclin-dependent kinase. J Med Chem 2000; 43(15): 2797-804.
48. Davies TG, Bentley J, Arris CE, Boyle FT, Curtin NJ, Endicott JA, et al. - Structure-based design of a potent purine-based cyclin-dependent kinase. Nat Struct Biol 2002; 9(10): 745-9.
49. Tibbles H, Vassilev A, Uckun FM. A dual function anti-leukemic agent with anti-thrombotic activity. Leuk Lymphoma 2002; 43(5): 1121-7.
50. Uckun FM, Vassilev A, Bartell S, Zheng Y, Mahajan S, Tibbles H. The Anti-leukemia Bruton's Tyosine Kinase Inhibitor alpha-cyano-Beta-methyl-N-(2,5-dibromophenyl) Propenamide (LFM-A13) Prevents Fatal Thromboembolism. Leukemia & Lymphoma 2003; 44(9): 1569-1577.
51. Tibbles HE, Samuel P, Erbeck D, Mahajan S, Uckun FM. In Vivo Toxicity and Anti-Thrombotic Profile of the Oral Formulation of the Anti-Leukemic Agent, LFM-A13-F. Arzneimittel-Forschung/Drug Research Accepted/In Press 2004.
52. Cetkovic-Cvrlje M, Draget AL, Uckun FM. Prevention of Islet Allograft Rejection in Diabetic Mice by Targeting Janus Kinase 3 with [4-(4′-Hydroxyphenyl)-amino-6,7-dimethoxyquinazoline] (JANEX-1). Arzeim.-Forsch./Drug Research 2003; In Press.
53. Narla RK, Liu X-P, Klis D, Uckun FM. Inhibition of human glioblastoma cell adhesion and invasion by 4-(4′-hydroxylphenyl)-amino-6,7-dimethoxyquinazoline (WHI-P131) and 4-(3′-bromo-4′-hydroxylphenyl)-amino-6,7-dimethoxyquinazoline (WHI-P154). Clin Can Res 1998; 4: In press.
54. Thompson JE, Cubbon RM, Cummings RT, Wicker LS, Frankshun R, Cunningham BR, et al. Photochemical preparation of a pyridone containing tetracycle: AJak protein kinase inhibitor. Bioorg Med Chem Lett 2002; 12(8): 1219-23.
55. Burke WM, Jin X, Lin HJ, Huang M, Liu R, Reynolds RK, et al. Inhibition of constitutively active Stat3 suppresses growth of human ovarian and breast cancer cells. Oncogene 2001; 20(55): 7925-34.
56. Behbod F, Erwin-Cohen RA, Wang ME, Trawick BW, Qu X, Varani R, et al. Concomitant inhibition of Janus kinase 3 and calcineurin-dependent signaling pathways synergistically prolongs the survival of rat heart allografts. J Immunol 2001; 166(6): 3724-32.
57. Adjei AA. Ras signaling pathway proteins as therapeutic targets. Curr Pharm Design 2001; 7(16): 1581-94.
58. Metcalf CA 3rd, van Schravendijk MR, Dalgarno DC, Sawyer TK. Targeting protein kinases for bone disease: Discovery and development of Src inhibitors. Curr Pharm Design 2002; 8(23): 2049-75.
59. Uckun FM. Rationally designed anti-mitotic agents with pro-apoptotic activity. Curr Pharm Design 2001; 7(16): 1627-39.