Human kinome drug discovery and the emerging importance of atypical allosteric inhibitors

Expert Opinion on Drug Discovery

Volumn 5, Issue 3, 2010, Pages 277-290

  Eglen, Richard M ^a   Reisine, Terry ^a  

^a PERKINELMER INC   (United States)

Author keywords

Allosteric; Allosterism; Assay; Discovery; High throughput screening; Kinase; Kinome; Protein redistribution; Protein translocation

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; 4 (2 AMINOETHYLAMINO) 1,8 DIMETHYLIMIDAZO[1,2 A]QUINOXALINE; AAL 993; CYCLIN DEPENDENT KINASE; DASATINIB; ERLOTINIB; GEFITINIB; I KAPPA B KINASE; IMATINIB; LAPATINIB; NILOTINIB; PROTEIN KINASE; PROTEIN KINASE INHIBITOR; SORAFENIB; SUNITINIB; TEMSIROLIMUS; UNCLASSIFIED DRUG;

ALLOSTERISM; DRUG ACTIVITY; ENZYME ANALYSIS; ENZYME INHIBITION; HIGH THROUGHPUT SCREENING; HUMAN; NONHUMAN; PRIORITY JOURNAL; REVIEW;

EID: 77749329022     PISSN: 17460441     EISSN: None     Source Type: Journal    
DOI: 10.1517/17460441003636820     Document Type: Review

References (92)

1. Carter C, Kane C. Therapeutic potential of natural compounds that regulate the activity of protein kinase C. Curr Med Chem 2004;11:2883-2902
2. Lapenna S, Giordano A. Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov 2009;8:547-566
3. Cohen P. Protein kinases - the major drug targets of the twenty-first century? Nat Rev Drug Discov 2002;1:309-315
4. Ghosh S, Liu X-P, Zheng Y, et al. Rational design of potent and selective EGFR tyrosine kinase inhibitors as anticancer agents. Curr Cancer Drug Targets 2001;1:129-140
5. Manning G, Whyte DB, Martinez R, et al. The protein kinase complement of the human genome. Science 2002;298:1912-2234
6. Cohen P. The role of protein phosphorylation in human health and disease. The Sir Hans Krebs Medal Lecture. Eur J Biochem 2001;268:5001-5010
7. Nestler E, Greengard P. Protein phosphorylation in the brain. Nature 1983;305:583-588
8. Uckun F, Mao C. Tyrosine kinases as new molecular targets in treatment of inflammatory disorders and leukemia. Curr Pharm Des 2004;10:1083-1091
9. Knuutila S, Bjorkqvist AM, Autio K, et al. DNA copy number amplifications in human neoplasms: review of comparative genomic hybridization studies. Am J Path 1998;152:1107-1123 (Pubitemid 28221862)
10. Noble M, Endicott J, Johnson L. Protein kinase inhibitors: insights into drug design from structure. Science 2004;303:1800-1805
11. Dancy J, Sausville EA. Issues and progress with protein kinase inhibitors for cancer treatment. Nat Rev Drug Discov 2003;2:296-313
12. DiGiovanna MP, Stern DF, Edgerton SM, et al. Relationship of epidermal growth factor receptor expression to ErbB-2 signaling activity and prognosis in breast cancer patients J Clin Oncol 2005;23:1152-1160
13. Piccart-Gebhart M, Procter M, Leyland-Jones B, et al. Herceptin Adjuvant (HERA) Trial Study Team. N Engl J Med 2005;353:1659-1672
14. Druker B, Tamura S, Buchdunger E, et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med 1996;2:561-566
15. Druker B, Talpaz M, Resta D, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 2001;344:1031-1037
16. Barker AJ, Gibson KH, Grundy W, et al. Studies leading to the identification of ZD1839 (IRESSA): an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor targeted to the treatment of cancer. Bioorg Med Chem Lett 2001;11:1911-1914
17. Hidalgo M, Eckhardt SG. Matrix metalloproteinase inhibitors: how can we optimize their development? Ann Oncol 2001;12:285-287 (Pubitemid 32288682)
18. Druker BJ. STI571 (Gleevec) as a paradigm for cancer therapy Trends Mol Med 2002; 8:S14-18
19. Eglen RM, Reisine T. The current status of drug discovery against the human kinome. Assays Drug Dev Technol 2009;7:22-43
20. Zhang J, Yang P, Gray N. Targeting cancer with small molecule kinase inhibitors. Nat Rev Cancer 2009;9:28-39
21. Li B, Liu Y, Uno T, Gray N. Creating chemical diversity to target protein kinases. Comb Chem High Throughput Screen 2004;7(5):453-472
22. Walker E, Pacold M, Perisic O, et al. Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine Mol Cell 2000;6:909-919
23. Blackwell LJ, et al. High-throughput screening of the cyclic AMP-dependent protein kinase (PKA) Using the Caliper microfluidic platform. Methods Mol Biol 2009;565:225-237
24. Hacker C, et al. In-house kinase selectivity profiling using microfluidics. Available from: http://www.caliperls.com/assets/ 017/7525.pdf
25. Comess KM, et al. Kinase drug discovery by affinity selection/mass spectrometry (ASMS): application to DNA damage checkpoint kinase Chk1. J Biomol Screen 2006;11:755-764
26. Nagar B, Bornmann WG, Pellicena P, et al. Crystal structures of the kinase domain of c-Abl in complex with the small molecule inhibitors PD173955 and imatinib (STI-571). Cancer Research, 2002;62:4236-4243
27. Nagar B. Cancer Drug Imatinab (Gleevec/ STI-571). J Nutr 2007;137:1518S-23S
28. Lee GM, Craik CS. Trapping moving targets with small molecules. Science 2009;324:213-215
29. Simard JR. et al. Development of a fluorescent tagged kinase assay system for the detection and characterization of allosteric kinase inhibitors. JACS 2009;131:13286-13296
30. Simard JR, et al. A new screening assay for allosteric inhibitors of cSrc. Nat. Chem Biol 2009;5:394-396
31. Shen G. Selective protein kinase C inhibitors and their applications. Curr Drug Targets Cardiovasc Haematol Disord 2003;3:301-307
32. Kim C, Cheng C Y, Saldanha SA, Taylor SS. PKA-I holoenzyme structure reveals a mechanism for cAMP-dependent activation. Cell 2007;130:1032-1043
33. Karin M, Yamamoto Y, Wang Q. The IKK NF-kappa B system: a treasure trove for drug development. Nat Rev Drug Discov 2004;3:17-26
34. May M, Ghosh S. IkB kinases: kinsmen with different crafts. Science 1999;284:271-273
35. Barnes PJ, Karin M. Nuclear factor-kB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 1997;336:1066-1071
36. Haefner B. NF-kB: arresting a major culprit in cancer. Drug Discov Today 2002;7:653-663
37. Karin M, Lin A. NF-kB at the crossroads of life and death. Nature Immunol 2002;3:221-227
38. May M, D'Acquisto F, Madge L, et al. Selective inhibition of NFkB activation by a peptide that blocks the interaction of NEMO with the IkB kinase complex. Science 2000;289:1550-1554
39. Burke JR, et al. BMS-345541 is a highly selective inhibitor of IkB kinase that binds at an allosteric site of the enzyme and blocks NF-kB-dependent transcription in mice. J Biol Chem 2003;278:1450-1456
40. Gillooly KM, et al. Periodic, partial inhibition of IKKbeta-mediated signaling yields therapeutic benefit in preclinical models of rheumatoid arthritis. JPET 2009. Published on August 3, 2009 as doi: 10.1124/jpet.109. 156018
41. Knockaert M, Greengard P, Meijer L. Pharmacological inhibitors of cyclin-dependent kinases. Trends Pharm Sci 2002;23:417-425
42. Malumbres M, Pevarello P, Barbacid M, Bischoff JR. CDK inhibitors in cancer therapy: what is next? Trends Pharmacol Sci 2008;29:16-21
43. Jeffrey P, Tong L, Pavletich N. Structural basis of inhibition of CDK-cyclin complexes by INK4 inhibitors. Genes Dev 2000;14:3115-3125
44. Marsden B, Knapp S. Doing more than just the structure-structural genomics in kinase drug discovery. Curr Opin Chem Biol 2008;12:40-45
45. Pavletich NP. Mechanisms of cyclin-dependent kinase regulation: structures of Cdks, their cyclin activators, and Cip and INK4 inhibitors J Mol Biol 1999;287:821-828
46. Parry D, Bates S, Mann DJ, Peters G. Lack of cyclin D-Cdk complexes in Rb-negative cells correlates with high levels of p16INK4/MTS1 tumour suppressor gene product. EMBO J 1995;14:503-511
47. Hall M, Peters G. Genetic alterations of cyclins, cyclin-dependent kinases, and Cdk inhibitors in human cancer. Adv Cancer Res 1996;68:67-108
48. Zuo L, Weger J, Yang Q, et al. Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma. Nat Genet 1996;12:97-99
49. Adrian FJ, et al. Allosteric inhibitors of Bcr-abl-dependent cell proliferation. Nat Chem Biol 2006;2:95-102
50. Lindsley CW, et al. The PI3K/Akt pathway: recent progress in the development of ATP-competitive and allosteric Akt kinase inhibitors [review]. Curr Cancer Drug Targets 2008;8(1):7-18
51. Bogoyevitch MA, Fairlie DP. A new paradigm for protein kinase inhibition: blocking phosphorylation without directly targeting the ATP binding site. Drug Discov Today 2007;12(15-16):622-633
52. El Abdellaoui H, Varaprasad CV, Barawkar D, et al. Identification of isothiazole-4-carboxamidine derivative as a novel class of allosteric MEK1 inhibitors. Bioorg Med Chem Lett 2006;16:5561-5566
53. Mussmann R, Geese M, Harder F, et al. Inhibition of GSK3 promotes replication and survival of pancreatic beta cells. J Biol Chem 2007;282:12030-12037
54. Vassilev LT, et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 2004;303:844-848
55. Haupt Y, Maya R, Kazaz A, et al. Mdm2 promotes rapid degradation of p53. Nature 1997;387:296-299
56. Domling A. Small molecular weight protein-protein interaction antagonists-an insurmountable challenge? Current Opinion in Chemical Biology 2008;12:1-11
57. Best JL, Amezcua CA, Mayr B, et al. Identification of small molecule antagonists that inhibit an activator: coactivator interaction. Proc Natl Acad Sci USA 2004;101:17622-17627
58. Converso A, Hartingh T, Garbaccio RM, et al. Development of thioquinazolinones, allosteric Chk1 kinase inhibitors. Bioorg Med Chem Lett 2009;19:1240-1244
59. Han S, Zhou V, Pan S, et al. Identification of coumarin derivatives as a novel class of allosteric MEK1 inhibitors. Bioorg Med Chem Lett 2005;15:5467-5473
60. Schroter T, Minond D, Weiser A, et al. Comparison of miniaturized time-resolved fluorescence resonance energy transfer and enzyme-coupled luciferase high-throughput screening assays to discover inhibitors of Rho-kinase II (ROCK-II). J Biomol Screen 2008;13:17-28
61. Braunwalder AF, Yarwood DR, Sills MA, Lipson KE. Measurement of the protein tyrosine kinase activity of c-src using time-resolved fluorometry of europium chelates. Anal Biochem 1996;238:159-164
62. Olive DM. Quantitative methods for the analysis of protein phosphorylation in drug development. Expert Rev Proteomics 2004;1:327-341
63. Zhang WG, Shor B, Yu K. Identification and characterization of a constitutively T-loop phosphorylated and active recombinant S6K1: expression, purification, and enzymatic studies in a high capacity non-radioactive TR-FRET Lance assay. Protein Expr Purif 2006;46:414-420
64. Rodems SM, Hamman BD, Lin C, et al. A FRET-based assay platform for ultra-high density drug screening of protein kinases and phosphatases. Assay Drug Dev Technol 2002;1:9-19
65. Mathis G. HTRF(R) technology. J Biomol Screen 1999;4:309-314
66. Rushe M, Silvian L, Bixler S, et al. Structure of a NEMO/IKK-associating domain reveals architecture of the interaction site. Structure 2008;16:798-805
67. Warner G, Illy C, Pedro L, et al. AlphaScreen kinase HTS platforms Curr Med Chem, 2004;11:721-730
68. Chen T, Kablaoui N, Little J, et al. Identification of small-molecule inhibitors of the JIP-JNK interaction. Biochem J 2009;420:283-294
69. Gupta S, Barrett T, Whitmarsh AJ, et al. Selective interaction of JNK protein kinase isoforms with transcription factors. EMBO J 1996;15:2760-2770
70. Manning A, Davis R. Targeting JNK for therapeutic benefit: from junk to gold? Nat Drug Discov 2003;2:554-565
71. Bennett B, Sasaki D, Murray B, et al. SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proc Natl Acad Sci USA 2001;98:13681-13686
72. Hirosumi J, Tuncman G, Chang L, et al. A central role for JNK in obesity and insulin resistance. Nature 2002;420:333-336
73. Seethala R, Menzel R. A fluorescence polarization competition immunoassay for tyrosine kinases. Anal Biochem 1998;255:257-262
74. Fedorov O, Marsden B, Pogacic V, et al. A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. PNAS 2007;104:20523-20528
75. Prinz A, Diskar M, Herberg FW. Application of bioluminescence resonance energy transfer (BRET) for biomolecular interaction studies. Chembiochem 2006;7:1007-1012
76. Stefan E, Aquin S, Berger N, et al. Quantification of dynamic protein complexes using Renilla luciferase fragment complementation applied to protein kinase A activities in vivo. Proc Natl Acad Sci USA 2007;104:16916-16921
77. Fujioka A, Terai K, Itoh R, et al. Dynamics of the Ras/ERK MAPK cascade as monitored by fluorescent probes. J Biol Chem 2006;281:8917-8926
78. Remy I, Michnick S. Clonal selection and in vivo quantitation of protein interactions with protein-fragment complementation assays. Proc Natl Acad Sci USA 1999;96:5394-5399
79. Perillan P, Chen M, Potts E, Simard J. Transforming growth factor-beta 1 regulates Kir2.3 inward rectifier K + channels via phospholipase C and protein kinase C-delta in reactive astrocytes from adult rat brain. J Biol Chem 2002;277:1974-1980
80. Majumder P, Mishra N, Sun X, et al. Targeting of protein kinase C delta to mitochondria in the oxidative stress response. Cell Growth Differ 2001;9:465-470
81. O'Flaherty J, Chadwell BA, Kearns MW, et al. Protein kinases C translocation responses to low concentrations of arachidonic acid. J Biol Chem 2001;276:24743-24750
82. Gasparri F, Sola F, Bandiera T, et al. High-content analysis of kinase activity in cells. Comb Chem High throughput Screen 2008;11:523-536
83. Palo K, Brand L, Eggeling C, et al. Fluorescence intensity and lifetime distribution analysis: toward higher accuracy in fluorescence fluctuation spectroscopy. Biophys J 2002;83:605-618
84. Trask OJ, Nickischer D, Burton A, et al. High-throughput automated confocal microscopy imaging screen of a kinase-focused library to identify p38 mitogen-activated protein kinase inhibitors using the GE InCell 3000 analyzer. Methods Mol Biol 2009;565:159-186
85. Almholt DL, Loechel F, Nielsen SJ, et al. Nuclear export inhibitors and kinase inhibitors identified using a MAPK-activated protein kinase 2 redistribution screen. Assay Drug Dev Technol 2004;2:7-20
86. Wolff M, Haasen D, Merk S, et al. Automated high content screening for phosphoinositide 3 kinase inhibition using an AKT1 redistribution assay. Comb Chem High Throughput Screen 2006;9:339-350
87. Michnick SW, MacDonald ML, Westwick JK. Chemical genetic strategies to delineate map kinase signaling pathways using protein fragment complementation assays (PCA). Methods 2006;40:287-293
88. Gallegos L, Kunkel M, Newton A. Targeting protein kinase C activity reporter to discrete intracellular regions reveals spatiotemporal differences in agonist-dependent signaling. J Biol Chem 2006;281:30947-30956
89. Corbin A, La Rosee P, Stoffregen E, et al. Several Bcr-Abl kinase domain mutants associated with imatinib mesylate resistance remain sensitive to imatinib. Blood 2003;101:4611
90. Gorre M, Mohammed M, Ellwood K, et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 2001;293:876
91. Eglen R, Gilchrist A, Reisine T. An overview of high throughput screening using primary and embryonic stem cells. Comb Chem High Throughput Screen 2008;11:566-572
92. Eglen R, Reisine T. New insights into GPCR function: implications for HTS [review]. Methods Mol Biol 2009;552:1-13