PIM1 kinase as a target for cancer therapy

Expert Opinion on Investigational Drugs

Volumn 21, Issue 4, 2012, Pages 425-436

  Merkel, Anna Lena ^a   Meggers, Eric ^a   Ocker, Matthias ^a  

^a PHILIPPS UNIVERSITY MARBURG   (Germany)

Author keywords

Cancer; Inhibitors; Metal complexes; PIM1; Serine threonine kinase

Indexed keywords

[1,2,4]TRIAZOLO[4,3 B]PYRIDAZIN; ADENOSINE TRIPHOSPHATE; BENZO[4,5]THIENO[3,2 D]PYRIMIDINONE; BENZO[C][2,6]NAPHTHYRIDINE; BENZO[C]ISOXAZOLE; BISINDOLYLMALEIMIDE; DIPYRONE; ENZYME INHIBITOR; IMIDAZO[1,2 B]PYRIDAZIN; ISOXAZOLE DERIVATIVE; ISOXAZOLO[3,4 B]QUINOLINEDIONE; NAPHTHYRIDINE DERIVATIVE; ORGANOMETALLIC COMPOUND; PROTEIN KINASE PIM 1; PROTEIN KINASE PIM 1 INHIBITOR; PYRIDAZINE DERIVATIVE; PYRIMIDINONE DERIVATIVE; QUINOLINE DERIVATIVE; STAUROSPORINE; THIAZOLIDINE 2,4 DIONE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; CANCER CHEMOTHERAPY; DRUG MECHANISM; DRUG TARGETING; ENZYME INHIBITION; ENZYME REGULATION; HUMAN; NEOPLASM; NONHUMAN; PROGNOSIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SYSTEMATIC REVIEW;

ANIMALS; HUMANS; MOLECULAR TARGETED THERAPY; NEOPLASMS; PROTEIN KINASE INHIBITORS; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS C-PIM-1;

EID: 84858238737     PISSN: 13543784     EISSN: 17447658     Source Type: Journal    
DOI: 10.1517/13543784.2012.668527     Document Type: Review

References (122)

1. Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893-917
2. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010;60:277-300
3. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000;100:57-70 (Pubitemid 30046295)
4. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144:646-74
5. Stegmeier F, Warmuth M, Sellers WR, Dorsch M. Targeted cancer therapies in the twenty-first century: lessons from imatinib. Clin Pharmacol Ther 2010;87:543-52
6. Steeghs N, Nortier JW, Gelderblom H. Small molecule tyrosine kinase inhibitors in the treatment of solid tumors: an update of recent developments. Ann Surg Oncol 2007;14:942-53 (Pubitemid 46175346)
7. Fabian MA, Biggs WH III, Treiber DK, et al. A small molecule-kinase interaction map for clinical kinase inhibitors. Nat Biotechnol 2005;23:329-36 (Pubitemid 41094421)
8. Mabuchi S, Hisamatsu T, Kimura T. Targeting mTOR signaling pathway in ovarian cancer. Curr Med Chem 2011;18:2960-8
9. Sparks CA, Guertin DA. Targeting mTOR: prospects for mTOR complex 2 inhibitors in cancer therapy. Oncogene 2010;29:3733-44
10. Workman P, Clarke PA, Raynaud FI, van Montfort RL. Drugging the PI3 kinome: from chemical tools to drugs in the clinic. Cancer Res 2010;70:2146-57
11. Strebhardt K. Multifaceted polo-like kinases: drug targets and antitargets for cancer therapy. Nat Rev Drug Discov 2010;9:643-60
12. McInnes C, Wyatt MD. PLK1 as an oncology target: current status and future potential. Drug Discov Today 2011;16:619-25
13. Lens SM, Voest EE, Medema RH. Shared and separate functions of polo-like kinases and aurora kinases in cancer. Nat Rev Cancer 2010;10:825-41
14. Katayama H, Sen S. Aurora kinase inhibitors as anticancer molecules. Biochim Biophys Acta 2010;1799:829-39
15. Dar AA, Goff LW, Majid S, et al. Aurora kinase inhibitors-rising stars in cancer therapeutics? Mol Cancer Ther 2010;9:268-78
16. Plentz RR, Manns MP, Greten TF. Molecular therapy of pancreatic cancer. Minerva Endocrinol 2010;35:27-33
17. Reddy D, Wainberg ZA. Targeted therapies for metastatic esophagogastric cancer. Curr Treat Options Oncol 2011;12:46-60
18. Greten TF, Korangy F, Manns MP, Malek NP. Molecular therapy for the treatment of hepatocellular carcinoma. Br J Cancer 2009;100:19-23
19. Jakobsen JN, Sorensen JB. Review on clinical trials of targeted treatments in malignant mesothelioma. Cancer Chemother Pharmacol 2011;68:1-15
20. Sherman SI. Targeted therapies for thyroid tumors. Mod Pathol 2011;24(Suppl 2):S44-52
21. Shah N, Pang B, Yeoh KG, et al. Potential roles for the PIM1 kinase in human cancer-a molecular and therapeutic appraisal. Eur J Cancer 2008;44:2144-51
22. Nawijn MC, Alendar A, Berns A. For better or for worse: the role of pim oncogenes in tumorigenesis. Nat Rev Cancer 2011;11:23-34
23. Cuypers HT, Selten G, Quint W, et al. Murine leukemia virus-induced T-cell lymphomagenesis: integration of proviruses in a distinct chromosomal region. Cell 1984;37:141-50 (Pubitemid 14079845)
24. Hoover D, Friedmann M, Reeves R, Magnuson NS. Recombinant human pim-1 protein exhibits serine/threonine kinase activity. J Biol Chem 1991;266:14018-23 (Pubitemid 21907455)
25. Saris CJ, Domen J, Berns A. The pim-1 oncogene encodes two related protein-serine/threonine kinases by alternative initiation at AUG and CUG. EMBO J 1991;10:655-64 (Pubitemid 21905520)
26. Wang Z, Bhattacharya N, Weaver M, et al. Pim-1: a serine/threonine kinase with a role in cell survival, proliferation, differentiation and tumorigenesis. J Vet Sci 2001;2:167-79
27. Miura O, Miura Y, Nakamura N, et al. Induction of tyrosine phosphorylation of vav and expression of pim-1 correlates with Jak2-mediated growth signaling from the erythropoietin receptor. Blood 1994;84:4135-41 (Pubitemid 24371915)
28. Zhu N, Ramirez LM, Lee RL, et al. CD40 signaling in B cells regulates the expression of the Pim-1 kinase via the NF-kappa B pathway. J Immunol 2002;168:744-54 (Pubitemid 34049575)
29. Magistroni V, Mologni L, Sanselicio S, et al. ERG deregulation induces PIM1 over-expression and aneuploidy in prostate epithelial cells. PLoS One 2011;6:e28162
30. Nasser MW, Datta J, Nuovo G, et al. Down-regulation of micro-RNA-1 (miR-1) in lung cancer. Suppression of tumorigenic property of lung cancer cells and their sensitization to doxorubicin-induced apoptosis by miR-1. J Biol Chem 2008;283:33394-405
31. Thomas M, Lange-Grunweller K, Weirauch U, et al. The proto-oncogene pim-1 is a target of miR-33a. Oncogene 2012;31:918-28
32. Eiring AM, Harb JG, Neviani P, et al. miR-328 functions as an RNA decoy to modulate hnRNP E2 regulation of mRNA translation in leukemic blasts. Cell 2010;140:652-65
33. Qian KC, Wang L, Hickey ER, et al. Structural basis of constitutive activity and a unique nucleotide binding mode of human pim-1 kinase. J Biol Chem 2005;280:6130-7 (Pubitemid 40280098)
34. Liang H, Hittelman W, Nagarajan L. Ubiquitous expression and cell cycle regulation of the protein kinase PIM-1. Arch Biochem Biophys 1996;330:259-65
35. Bullock AN, Debreczeni J, Amos AL, et al. Structure and substrate specificity of the pim-1 kinase. J Biol Chem 2005;280:41675-82 (Pubitemid 43000572)
36. Kim O, Jiang T, Xie Y, et al. Synergism of cytoplasmic kinases in IL6-induced ligand-independent activation of androgen receptor in prostate cancer cells. Oncogene 2004;23:1838-44 (Pubitemid 38445409)
37. Shay KP, Wang Z, Xing PX, et al. Pim-1 kinase stability is regulated by heat shock proteins and the ubiquitin-proteasome pathway. Mol Cancer Res 2005;3:170-81 (Pubitemid 40524900)
38. Losman JA, Chen XP, Vuong BQ, et al. Protein phosphatase 2A regulates the stability of pim protein kinases. J Biol Chem 2003;278:4800-5 (Pubitemid 36800983)
39. Mochizuki T, Kitanaka C, Noguchi K, et al. Physical and functional interactions between pim-1 kinase and Cdc25A phosphatase. Implications for the pim-1-mediated activation of the c-Myc signaling pathway. J Biol Chem 1999;274:18659-66
40. Bachmann M, Kosan C, Xing PX, et al. The oncogenic serine/threonine kinase pim-1 directly phosphorylates and activates the G2/M specific phosphatase Cdc25C. Int J Biochem Cell Biol 2006;38:430-43 (Pubitemid 41821890)
41. Bachmann M, Hennemann H, Xing PX, et al. The oncogenic serine/threonine kinase pim-1 phosphorylates and inhibits the activity of Cdc25C-associated kinase 1 (C-TAK1): a novel role for Pim-1 at the G2/M cell cycle checkpoint. J Biol Chem 2004;279:48319-28 (Pubitemid 39540988)
42. Wang Z, Bhattacharya N, Mixter PF, et al. Phosphorylation of the cell cycle inhibitor p21Cip1/WAF1 by pim-1 kinase. Biochim Biophys Acta 2002;1593:45-55 (Pubitemid 35335911)
43. Morishita D, Katayama R, Sekimizu K, et al. Pim kinases promote cell cycle progression by phosphorylating and down-regulating p27Kip1 at the transcriptional and posttranscriptional levels. Cancer Res 2008;68:5076-85
44. Cen B, Mahajan S, Zemskova M, et al. Regulation of Skp2 levels by the pim-1 protein kinase. J Biol Chem 2010;285:29128-37
45. Schuppan D, Ocker M. Integrin-mediated control of cell growth. Hepatology 2003;38:289-91 (Pubitemid 36919848)
46. Bhattacharya N, Wang Z, Davitt C, et al. Pim-1 associates with protein complexes necessary for mitosis. Chromosoma 2002;111:80-95 (Pubitemid 36067383)
47. Aho TL, Sandholm J, Peltola KJ, et al. Pim-1 kinase promotes inactivation of the pro-apoptotic Bad protein by phosphorylating it on the Ser112 gatekeeper site. FEBS Lett 2004;571:43-9 (Pubitemid 38992921)
48. Gu JJ, Wang Z, Reeves R, Magnuson NS. PIM1 phosphorylates and negatively regulates ASK1-mediated apoptosis. Oncogene 2009;28:4261-71
49. Zhang F, Beharry ZM, Harris TE, et al. PIM1 protein kinase regulates PRAS40 phosphorylation and mTOR activity in FDCP1 cells. Cancer Biol Ther 2009;8:846-53
50. Jung CH, Ro SH, Cao J, et al. mTOR regulation of autophagy. FEBS Lett 2010;584:1287-95
51. Chen J, Kobayashi M, Darmanin S, et al. Hypoxia-mediated up-regulation of pim-1 contributes to solid tumor formation. Am J Pathol 2009;175:400-11
52. Brault L, Gasser C, Bracher F, et al. PIM serine/threonine kinases in the pathogenesis and therapy of hematologic malignancies and solid cancers. Haematologica 2010;95:1004-15
53. Zippo A, De Robertis A, Serafini R, Oliviero S. PIM1-dependent phosphorylation of histone H3 at serine 10 is required for MYC-dependent transcriptional activation and oncogenic transformation. Nat Cell Biol 2007;9:932-44 (Pubitemid 47190448)
54. Hogan C, Hutchison C, Marcar L, et al. Elevated levels of oncogenic protein kinase pim-1 induce the p53 pathway in cultured cells and correlate with increased Mdm2 in mantle cell lymphoma. J Biol Chem 2008;283:18012-23
55. Zemskova M, Lilly MB, Lin YW, et al. p53-dependent induction of prostate cancer cell senescence by the PIM1 protein kinase. Mol Cancer Res 2010;8:1126-41
56. Xie Y, Xu K, Linn DE, et al. The 44-kDa pim-1 kinase phosphorylates BCRP/ABCG2 and thereby promotes its multimerization and drug-resistant activity in human prostate cancer cells. J Biol Chem 2008;283:3349-56
57. Chen J, Kobayashi M, Darmanin S, et al. Pim-1 plays a pivotal role in hypoxia-induced chemoresistance. Oncogene 2009;28:2581-92
58. Grundler R, Brault L, Gasser C, et al. Dissection of PIM serine/threonine kinases in FLT3-ITD-induced leukemogenesis reveals PIM1 as regulator of CXCL12-CXCR4-mediated homing and migration. J Exp Med 2009;206:1957-70
59. van Lohuizen M, Verbeek S, Krimpenfort P, et al. Predisposition to lymphomagenesis in pim-1 transgenic mice: cooperation with c-myc and N-myc in murine leukemia virus-induced tumors. Cell 1989;56:673-82 (Pubitemid 19065532)
60. Verbeek S, van Lohuizen M, van der Valk M, et al. Mice bearing the E mu-myc and E mu-pim-1 transgenes develop pre-B-cell leukemia prenatally. Mol Cell Biol 1991;11:1176-9 (Pubitemid 21895472)
61. Schenone S, Tintori C, Botta M. Using insights into pim1 structure to design new anticancer drugs. Curr Pharm Des 2010;16:3964-78
62. Amson R, Sigaux F, Przedborski S, et al. The human protooncogene product p33pim is expressed during fetal hematopoiesis and in diverse leukemias. Proc Natl Acad Sci USA 1989;86:8857-61 (Pubitemid 20010324)
63. Hsi ED, Jung SH, Lai R, et al. Ki67 and PIM1 expression predict outcome in mantle cell lymphoma treated with high dose therapy, stem cell transplantation and rituximab: a Cancer and Leukemia Group B 59909 correlative science study. Leuk Lymphoma 2008;49:2081-90
64. Mahadevan D, Spier C, Della Croce K, et al. Transcript profiling in peripheral T-cell lymphoma, not otherwise specified, and diffuse large B-cell lymphoma identifies distinct tumor profile signatures. Mol Cancer Ther 2005;4:1867-79 (Pubitemid 43056970)
65. Guo S, Mao X, Chen J, et al. Overexpression of pim-1 in bladder cancer. J Exp Clin Cancer Res 2010;29:161
66. Dhanasekaran SM, Barrette TR, Ghosh D, et al. Delineation of prognostic biomarkers in prostate cancer. Nature 2001;412:822-6 (Pubitemid 32801464)
67. Valdman A, Fang X, Pang ST, et al. Pim-1 expression in prostatic intraepithelial neoplasia and human prostate cancer. Prostate 2004;60:367-71 (Pubitemid 39050657)
68. Cibull TL, Jones TD, Li L, et al. Overexpression of pim-1 during progression of prostatic adenocarcinoma. J Clin Pathol 2006;59:285-8 (Pubitemid 43344891)
69. Xu Y, Zhang T, Tang H, et al. Overexpression of PIM-1 is a potential biomarker in prostate carcinoma. J Surg Oncol 2005;92:326-30 (Pubitemid 41779291)
70. He HC, Bi XC, Zheng ZW, et al. Real-time quantitative RT-PCR assessment of PIM-1 and hK2 mRNA expression in benign prostate hyperplasia and prostate cancer. Med Oncol 2009;26:303-8
71. Liu HT, Wang N, Wang X, Li SL. Overexpression of pim-1 is associated with poor prognosis in patients with esophageal squamous cell carcinoma. J Surg Oncol 2010;102:683-8
72. Yan B, Yau EX, Samanta S, et al. Clinical and therapeutic relevance of PIM1 kinase in gastric cancer. Gastric Cancer 2011 (Epub ahead of print)
73. Warnecke-Eberz U, Bollschweiler E, Drebber U, et al. Prognostic impact of protein overexpression of the proto-oncogene PIM-1 in gastric cancer. Anticancer Res 2009;29:4451-5
74. Sepulveda AR, Tao H, Carloni E, et al. Screening of gene expression profiles in gastric epithelial cells induced by Helicobacter pylori using microarray analysis. Aliment Pharmacol Ther 2002;16(Suppl 2):145-57 (Pubitemid 41771473)
75. Chang YT, Wu MS, Chang YJ, et al. Distinct gene expression profiles in gastric epithelial cells induced by different clinical isolates of Helicobacter pylori-implication of bacteria and host interaction in gastric carcinogenesis. Hepatogastroenterology 2006;53:484-90
76. Beier UH, Weise JB, Laudien M, et al. Overexpression of pim-1 in head and neck squamous cell carcinomas. Int J Oncol 2007;30:1381-7
77. Choi JY, Cho SI, Do NY, et al. Clinical significance of the expression of galectin-3 and pim-1 in laryngeal squamous cell carcinoma. J Otolaryngol Head Neck Surg 2010;39:28-34
78. Peltola K, Hollmen M, Maula SM, et al. Pim-1 kinase expression predicts radiation response in squamocellular carcinoma of head and neck and is under the control of epidermal growth factor receptor. Neoplasia 2009;11:629-36
79. Babel I, Barderas R, Diaz-Uriarte R, et al. Identification of tumor-associated autoantigens for the diagnosis of colorectal cancer in serum using high density protein microarrays. Mol Cell Proteomics 2009;8:2382-95
80. Warnecke-Eberz U, Bollschweiler E, Drebber U, et al. Frequent down-regulation of pim-1 mRNA expression in non-small cell lung cancer is associated with lymph node metastases. Oncol Rep 2008;20:619-24
81. Reiser-Erkan C, Erkan M, Pan Z, et al. Hypoxia-inducible proto-oncogene pim-1 is a prognostic marker in pancreatic ductal adenocarcinoma. Cancer Biol Ther 2008;7:1352-9
82. Qian J, Niu J, Li M, et al. In vitro modeling of human pancreatic duct epithelial cell transformation defines gene expression changes induced by K-ras oncogenic activation in pancreatic carcinogenesis. Cancer Res 2005;65:5045-53 (Pubitemid 40827312)
83. Xu D, Allsop SA, Witherspoon SM, et al. The oncogenic kinase Pim-1 is modulated by K-Ras signaling and mediates transformed growth and radioresistance in human pancreatic ductal adenocarcinoma cells. Carcinogenesis 2011;32:488-95
84. Zemskova M, Sahakian E, Bashkirova S, Lilly M. The PIM1 kinase is a critical component of a survival pathway activated by docetaxel and promotes survival of docetaxel-treated prostate cancer cells. J Biol Chem 2008;283:20635-44
85. Kim W, Youn H, Seong KM, et al. PIM1-activated PRAS40 regulates radioresistance in non-small cell lung cancer cells through interplay with FOXO3a, 14-3-3 and protein phosphatases. Radiat Res 2011;176:539-52
86. von Lindern M, van Agthoven T, Hagemeijer A, et al. The human pim-1 gene is not directly activated by the translocation (6;9) in acute nonlymphocytic leukemia. Oncogene 1989;4:75-9 (Pubitemid 19085072)
87. Pasqualucci L, Neumeister P, Goossens T, et al. Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas. Nature 2001;412:341-6 (Pubitemid 32691848)
88. Deutsch AJ, Fruhwirth M, Aigelsreiter A, et al. Primary cutaneous marginal zone B-cell lymphomas are targeted by aberrant somatic hypermutation. J Invest Dermatol 2009;129:476-9
89. Kumar A, Mandiyan V, Suzuki Y, et al. Crystal structures of proto-oncogene kinase Pim1: a target of aberrant somatic hypermutations in diffuse large cell lymphoma. J Mol Biol 2005;348:183-93 (Pubitemid 40461849)
90. Jacobs MD, Black J, Futer O, et al. Pim-1 ligand-bound structures reveal the mechanism of serine/threonine kinase inhibition by LY294002. J Biol Chem 2005;280:13728-34 (Pubitemid 40517268)
91. Bullock AN, Debreczeni JE, Fedorov OY, et al. Structural basis of inhibitor specificity of the human protooncogene proviral insertion site in moloney murine leukemia virus (PIM-1) kinase. J Med Chem 2005;48:7604-14 (Pubitemid 41698801)
92. Debreczeni JE, Bullock AN, Atilla GE, et al. Ruthenium half-sandwich complexes bound to protein kinase Pim-1. Angew Chem Int Ed Engl 2006;45:1580-5 (Pubitemid 44109229)
93. Bullock AN, Russo S, Amos A, et al. Crystal structure of the PIM2 kinase in complex with an organoruthenium inhibitor. PLoS One 2009;4:e7112
94. Cheney IW, Yan S, Appleby T, et al. Identification and structure-activity relationships of substituted pyridones as inhibitors of Pim-1 kinase. Bioorg Med Chem Lett 2007;17:1679-83 (Pubitemid 46274341)
95. Tong Y, Stewart KD, Thomas S, et al. Isoxazolo[3,4-b]quinoline-3,4(1H,9H) -diones as unique, potent and selective inhibitors for Pim-1 and Pim-2 kinases: chemistry, biological activities, and molecular modeling. Bioorg Med Chem Lett 2008;18:5206-8
96. Pierce AC, Jacobs M, Stuver-Moody C. Docking study yields four novel inhibitors of the protooncogene Pim-1 kinase. J Med Chem 2008;51:1972-5 (Pubitemid 351438879)
97. Grey R, Pierce AC, Bemis GW, et al. Structure-based design of 3-aryl-6-aminotriazolo[ 4,3-b]pyridazine inhibitors of pim-1 kinase. Bioorg Med Chem Lett 2009;19:3019-22
98. Xia Z, Knaak C, Ma J, et al. Synthesis and evaluation of novel inhibitors of pim-1 and pim-2 protein kinases. J Med Chem 2009;52:74-86
99. Tao ZF, Hasvold LA, Leverson JD, et al. Discovery of 3H-benzo[4,5] thieno[3,2-d] pyrimidin-4-ones as potent, highly selective, and orally bioavailable inhibitors of the human protooncogene proviral insertion site in moloney murine leukemia virus (PIM) kinases. J Med Chem 2009;52:6621-36
100. Akue-Gedu R, Rossignol E, Azzaro S, et al. Synthesis, kinase inhibitory potencies, and in vitro antiproliferative evaluation of new Pim kinase inhibitors. J Med Chem 2009;52:6369-81
101. Sliman F, Blairvacq M, Durieu E, et al. Identification and structure-activity relationship of 8-hydroxy-quinoline-7-carboxylic acid derivatives as inhibitors of pim-1 kinase. Bioorg Med Chem Lett 2010;20:2801-5
102. Lopez-Ramos M, Prudent R, Moucadel V, et al. New potent dual inhibitors of CK2 and pim kinases: discovery and structural insights. FASEB J 2010;24:3171-85
103. Miduturu CV, Deng X, Kwiatkowski N, et al. High-throughput kinase profiling: a more efficient approach toward the discovery of new kinase inhibitors. Chem Biol 2011;18:868-79
104. Pierre F, Stefan E, Nedellec AS, et al. 7-(4H-1,2,4-Triazol-3-yl)benzo[c] [2,6] naphthyridines: a novel class of pim kinase inhibitors with potent cell antiproliferative activity. Bioorg Med Chem Lett 2011;21:6687-92
105. Xiang Y, Hirth B, Asmussen G, et al. The discovery of novel benzofuran-2-carboxylic acids as potent Pim-1 inhibitors. Bioorg Med Chem Lett 2011;21:3050-6
106. Ren JX, Li LL, Zheng RL, et al. Discovery of novel pim-1 kinase inhibitors by a hierarchical multistage virtual screening approach based on SVM model, pharmacophore, and molecular docking. J Chem Inf Model 2011;51:1364-75
107. Pogacic V, Bullock AN, Fedorov O, et al. Structural analysis identifies imidazo[1,2-b]pyridazines as PIM kinase inhibitors with in vitro antileukemic activity. Cancer Res 2007;67:6916-24 (Pubitemid 47105539)
108. Holder S, Zemskova M, Zhang C, et al. Characterization of a potent and selective small-molecule inhibitor of the PIM1 kinase. Mol Cancer Ther 2007;6:163-72 (Pubitemid 46206679)
109. Amaravadi R, Thompson CB. The survival kinases Akt and Pim as potential pharmacological targets. J Clin Invest 2005;115:2618-24 (Pubitemid 41434384)
110. Blanco-Aparicio C, Collazo AM, Oyarzabal J, et al. Pim 1 kinase inhibitor ETP-45299 suppresses cellular proliferation and synergizes with PI3K inhibition. Cancer Lett 2011;300:145-53
111. Chen LS, Redkar S, Bearss D, et al. Pim kinase inhibitor, SGI-1776, induces apoptosis in chronic lymphocytic leukemia cells. Blood 2009;114:4150-7
112. Chen LS, Redkar S, Taverna P, et al. Mechanisms of cytotoxicity to Pim kinase inhibitor, SGI-1776, in acute myeloid leukemia. Blood 2011;118:693-702
113. Santio NM, Vahakoski RL, Rainio EM, et al. Pim-selective inhibitor DHPCC-9 reveals pim kinases as potent stimulators of cancer cell migration and invasion. Mol Cancer 2010;9:279
114. Magnuson NS, Wang Z, Ding G, Reeves R. Why target PIM1 for cancer diagnosis and treatment? Future Oncol 2010;6:1461-78
115. Hu XF, Li J, Vandervalk S, et al. PIM-1-specific mAb suppresses human and mouse tumor growth by decreasing PIM-1 levels, reducing Akt phosphorylation, and activating apoptosis. J Clin Invest 2009;119:362-75
116. Batra V, Maris JM, Kang MH, et al. Initial testing (stage 1) of SGI-1776, a PIM1 kinase inhibitor, by the pediatric preclinical testing program. Pediatr Blood Cancer 2011 (Epub ahead of print)
117. Mumenthaler SM, Ng PY, Hodge A, et al. Pharmacologic inhibition of Pim kinases alters prostate cancer cell growth and resensitizes chemoresistant cells to taxanes. Mol Cancer Ther 2009;8:2882-93
118. Mahalingam D, Espitia CM, Medina EC, et al. Targeting PIM kinase enhances the activity of sunitinib in renal cell carcinoma. Br J Cancer 2011;105:1563-73
119. Atilla-Gokcumen GE, Pagano N, Streu C, et al. Extremely tight binding of a ruthenium complex to glycogen synthase kinase 3. ChemBioChem 2008;9:2933-6
120. Maksimoska J, Williams DS, Atilla-Gokcumen GE, et al. Similar biological activities of two isostructural ruthenium and osmium complexes. Chem Eur J 2008;14:4816-22
121. Bregman H, Meggers E. Ruthenium half-sandwich complexes as protein kinase inhibitors: an N-succinimidyl ester for rapid derivatizations of the cyclopentadienyl moiety. Org Lett 2006;8:5465-8
122. Feng L, Geisselbrecht Y, Blanck S, et al. Structurally sophisticated octahedral metal complexes as highly selective protein kinase inhibitors. J Am Chem Soc 2011;133:5976-86