The centrosome as potential target for cancer therapy and prevention

Expert Opinion on Therapeutic Targets

Volumn 17, Issue 1, 2013, Pages 43-52

  Korzeniewski, Nina ^a   Hohenfellner, Markus ^a   Duensing, Stefan ^a  

^a UNIVERSITY OF HEIDELBERG   (Germany)

Author keywords

Cancer; Cancer prevention; Cancer therapy; Centrosome; Genomic instability

Indexed keywords

1 CYCLOPROPYL 3 [3 (5 MORPHOLINOMETHYL 1H BENZIMIDAZOL 2 YL) 1H PYRAZOL 4 YL]UREA; 4 (8 CYCLOPENTYL 7 ETHYL 5,6,7,8 TETRAHYDRO 5 METHYL 6 OXO 2 PTERIDINYLAMINO) 3 METHOXY N (1 METHYL 4 PIPERIDINYL)BENZAMIDE; 4 [[9 CHLORO 7 (2,6 DIFLUOROPHENYL) 5H PYRIMIDO[5,4 D][2]BENZAZEPIN 2 YL]AMINO]BENZOIC ACID; AG 024322; ALISERTIB; AT 7519; AURORA A KINASE; AURORA KINASE INHIBITOR; BAY 1000394; CYC 116; CYC 800; CYCLIN DEPENDENT KINASE; DAP 81; DINACICLIB; ENMD 2076; GSK 461364; HMN 214; INDIRUBIN; MK 5108; N [5 (5 TERT BUTYL 2 OXAZOLYLMETHYLTHIO) 2 THIAZOLYL]ISONIPECOTAMIDE; NMS 1; ON 019190; P 27600; PF 03814375; POLO LIKE KINASE; PROTEASOME INHIBITOR; RIGOSERTIB; ROSCOVITINE; TAK 960; TKM 080301; UNCLASSIFIED DRUG; UNINDEXED DRUG; VOLASERTIB;

ANEUPLOIDY; ANTINEOPLASTIC ACTIVITY; BREAST CANCER; CANCER CHEMOTHERAPY; CANCER GROWTH; CANCER PREVENTION; CELL DEATH; CELL DIVISION; CELL ORGANELLE; CENTRIOLE; CENTROSOME; DRUG TARGETING; HUMAN; NEOPLASM; PROSTATE CANCER; REVIEW;

CELL DEATH; CELL DIVISION; CENTROSOME; HUMANS; NEOPLASMS;

EID: 84871236120     PISSN: 14728222     EISSN: 17447631     Source Type: Journal    
DOI: 10.1517/14728222.2013.731396     Document Type: Review

References (109)

1. Duensing S, Munger K. Centrosome abnormalities, genomic instability and carcinogenic progression. Biochim Biophys Acta 2001;2(8):M81-8 (Pubitemid 32146548)
2. Boveri T. Concerning the origin of malignant tumours by Theodor Boveri. Translated and annotated by Henry Harris. J Cell Sci 2008;121(Suppl 1):1-84
3. Ganem NJ, Godinho SA, Pellman D. A mechanism linking extra centrosomes to chromosomal instability. Nature 2009;460(7252):278-82
4. Guerrero AA, Martinez AC, van Wely KH. Merotelic attachments and non-homologous end joining are the basis of chromosomal instability. Cell Div 2010;5:13
5. Nigg EA. Centrosome aberrations: cause or consequence of cancer progression? Nat Rev Cancer 2002;2:1-11
6. Lingle WL, Lutz WH, Ingle JN, et al. Centrosome hypertrophy in human breast tumors: implications for genomic stability and cell polarity. Proc Natl Acad Sci USA 1998;95(6):2950-5 (Pubitemid 28135835)
7. Pihan GA, Purohit A, Wallace J, et al. Centrosome defects and genetic instability in malignant tumors. Cancer Res 1998;58(17):3974-85 (Pubitemid 28405657)
8. D'Assoro AB, Barrett SL, Folk C, et al. Amplified centrosomes in breast cancer: A potential indicator of tumor aggressiveness. Breast Cancer Res Treat 2002;75(1):25-34
9. Duensing S, Duensing A, Crum CP, Munger K. Human papillomavirus type 16 E7 oncoprotein-induced abnormal centrosome synthesis is an early event in the evolving malignant phenotype. Cancer Res 2001;61(6):2356-60 (Pubitemid 32685804)
10. Pihan GA, Purohit A, Wallace J, et al. Centrosome defects can account for cellular and genetic changes that characterize prostate cancer progression. Cancer Res 2001;61(5):2212-19 (Pubitemid 32692050)
11. Lingle WL, Barrett SL, Negron VC, et al. Centrosome amplification drives chromosomal instability in breast tumor development. Proc Natl Acad Sci USA 2002;99(4):1978-83 (Pubitemid 34169000)
12. Azimzadeh J, Bornens M. Structure and duplication of the centrosome. J Cell Sci 2007;120(Pt 13):2139-42 (Pubitemid 47074119)
13. Loncarek J, Hergert P, Magidson V, Khodjakov A. Control of daughter centriole formation by the pericentriolar material. Nat Cell Biol 2008;10(3):322-8 (Pubitemid 351331019)
14. Piel M, Meyer P, Khodjakov A, et al. The respective contributions of the mother and daughter centrioles to centrosome activity and behavior in vertebrate cells. J Cell Biol 2000;149(2):317-30
15. Nigg EA, Stearns T. The centrosome cycle: centriole biogenesis, duplication and inherent asymmetries. Nat Cell Biol 2011;13(10):1154-60
16. Nigg EA. Centrosome aberrations: cause or consequence of cancer progression? Nat Rev Cancer 2002;2(11):815-25 (Pubitemid 37328900)
17. Duensing S, Munger K. Mechanisms of genomic instability in human cancer: insights from studies with human papillomavirus oncoproteins. Int J Cancer 2004;109(2):157-62 (Pubitemid 38240914)
18. Guarguaglini G, Duncan PI, Stierhof YD, et al. The forkhead-associated domain protein Cep170 interacts with Polo-like kinase 1 and serves as a marker for mature centrioles. Mol Biol Cell 2005;16(3):1095-107 (Pubitemid 40349548)
19. Duensing S, Lee LY, Duensing A, et al. The human papillomavirus type 16 E6 and E7 oncoproteins cooperate to induce mitotic defects and genomic instability by uncoupling centrosome duplication from the cell division cycle. Proc Natl Acad Sci USA 2000;97(18):10002-7
20. Duensing S, Duensing A, Flores ER, et al. Centrosome abnormalities and genomic instability by episomal expression of human papillomavirus type 16 in raft cultures of human keratinocytes. J Virol 2001;75(16):7712-16 (Pubitemid 32738029)
21. Duensing S, Munger K. Centrosome abnormalities and genomic instability induced by human papillomavirus oncoproteins. Prog Cell Cycle Res 2003;5:383-91
22. Scheffner M, Huibregtse JM, Vierstra RD, Howley PM. The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell 1993;75(3):495-505 (Pubitemid 23335075)
23. Dyson N, Howley PM, Munger K, Harlow E. The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science 1989;243(4893):934-7 (Pubitemid 19066153)
24. Duensing S, Munger K. Human papillomaviruses and centrosome duplication errors: modeling the origins of genomic instability. Oncogene 2002;21(40):6241-8
25. Korzeniewski N, Treat B, Duensing S. The HPV-16 E7 oncoprotein induces centriole multiplication through deregulation of Polo-like kinase 4 expression. Mol Cancer 2011;10:61
26. Duensing A, Chin A, Wang L, et al. Analysis of centrosome overduplication in correlation to cell division errors in high-risk human papillomavirus (HPV)- associated anal neoplasms. Virology 2008;372(1):157-64 (Pubitemid 351215468)
27. Duensing S, Duensing A, Lee DC, et al. Cyclin-dependent kinase inhibitor indirubin-3'-oxime selectively inhibits human papillomavirus type 16 E7-induced numerical centrosome anomalies. Oncogene 2004;23(50):8206-15 (Pubitemid 39531832)
28. Galimberti F, Thompson SL, Ravi S, et al. Anaphase catastrophe is a target for cancer therapy. Clin Cancer Res 2011;17(6):1218-22
29. Zimonjic D, Brooks MW, Popescu N, et al. Derivation of human tumor cells in vitro without widespread genomic instability. Cancer Res 2001;61(24):8838-44 (Pubitemid 34013898)
30. Duensing S, Lee BH, Dal Cin P, Munger K. Excessive centrosome abnormalities without ongoing numerical chromosome instability in a Burkitt's lymphoma. Mol Cancer 2003;2:30
31. Martin-Subero JI, Knippschild U, Harder L, et al. Segmental chromosomal aberrations and centrosome amplifications: pathogenetic mechanisms in Hodgkin and Reed-Sternberg cells of classical Hodgkin's lymphoma? Leukemia 2003;17(11):2214-19 (Pubitemid 37428389)
32. Khodjakov A, Cole RW, Oakley BR, Rieder CL. Centrosome-independent mitotic spindle formation in vertebrates. Curr Biol 2000;10(2):59-67 (Pubitemid 30079190)
33. Nedelec F, Surrey T, Karsenti E. Self-organisation and forces in the microtubule cytoskeleton. Curr Opin Cell Biol 2003;15(1):118-24 (Pubitemid 36044724)
34. Chan JY. A clinical overview of centrosome amplification in human cancers. Int J Biol Sci 2011;7(8):1122-44
35. Faggioli F, Vezzoni P, Montagna C. Single-cell analysis of ploidy and centrosomes underscores the peculiarity of normal hepatocytes. PLoS One 2011;6(10):e26080
36. Moudjou M, Lanotte M, Bornens M. The fate of the centrosome-microtubule network in monocyte-derived giant cells. J Cell Sci 1989;94(Pt 2):237-44 (Pubitemid 19272961)
37. Cizmecioglu O, Arnold M, Bahtz R, et al. Cep152 acts as a scaffold for recruitment of Plk4 and CPAP to the centrosome. J Cell Biol 2010;191(4):731-9
38. Habedanck R, Stierhof YD, Wilkinson CJ, Nigg EA. The Polo kinase Plk4 functions in centriole duplication. Nat Cell Biol 2005;7(11):1140-6
39. Kleylein-Sohn J, Westendorf J, Le Clech M, et al. Plk4-induced centriole biogenesis in human cells. Dev Cell 2007;13(2):190-202 (Pubitemid 47163610)
40. Tsou MF, Stearns T. Mechanism limiting centrosome duplication to once per cell cycle. Nature 2006;442(7105):947-51 (Pubitemid 44285953)
41. Tsou MF, Wang WJ, George KA, et al. Polo kinase and separase regulate the mitotic licensing of centriole duplication in human cells. Dev Cell 2009;17(3):344-54
42. Nasmyth K. Segregating sister genomes: The molecular biology of chromosome separation. Science 2002;297(5581):559-65 (Pubitemid 34815333)
43. Nakamura A, Arai H, Fujita N. Centrosomal A. and cohesin function in separase-regulated centriole disengagement. J Cell Biol 2009;187(5):607-14
44. Schockel L, Mockel M, Mayer B, et al. Cleavage of cohesin rings coordinates the separation of centrioles and chromatids. Nat Cell Biol 2011;13(8):966-72
45. Liu X, Lei M, Erikson RL. Normal cells, but not cancer cells, survive severe Plk1 depletion. Mol Cell Biol 2006;26(6):2093-108 (Pubitemid 43346913)
46. Guan R, Tapang P, Leverson JD, et al. Small interfering RNA-mediated Pololike kinase 1 depletion preferentially reduces the survival of p53-defective, oncogenic transformed cells and inhibits tumor growth in animals. Cancer Res 2005;65(7):2698-704 (Pubitemid 40490070)
47. Lapenna S, Giordano A. Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov 2009;8(7):547-66
48. Guderian G, Westendorf J, Uldschmid A, Nigg EA. Plk4 trans- autophosphorylation regulates centriole number by controlling betaTrCP-mediated degradation. J Cell Sci 2010;123(Pt 13):2163-9
49. Rogers GC, Rusan NM, Roberts DM, et al. The SCF Slimb ubiquitin ligase regulates Plk4/Sak levels to block centriole reduplication. J Cell Biol 2009;184(2):225-39
50. Korzeniewski N, Zheng L, Cuevas R, et al. Cullin 1 functions as a centrosomal suppressor of centriole multiplication by regulating polo-like kinase 4 protein levels. Cancer Res 2009;69(16):6668-75
51. Cunha-Ferreira I, Rodrigues-Martins A, Bento I, et al. The SCF/Slimb ubiquitin ligase limits centrosome amplification through degradation of SAK/PLK4. Curr Biol 2009;19(1):43-9
52. Korzeniewski N, Cuevas R, Duensing A, Duensing S. Daughter centriole elongation is controlled by proteolysis. Mol Biol Cell 2010;21(22):3942-51
53. Tetsu O, McCormick F. Proliferation of cancer cells despite CDK2 inhibition. Cancer Cell 2003;3(3):233-45 (Pubitemid 37443879)
54. Bornens M, Paintrand M, Berges J, et al. Structural and chemical characterization of isolated centrosomes. Cell Motil Cytoskeleton 1987;8(3):238-49
55. Wang WJ, Soni RK, Uryu K, Tsou MF. The conversion of centrioles to centrosomes: essential coupling of duplication with segregation. J Cell Biol 2011;193(4):727-39
56. O'Regan L, Blot J, Fry AM. Mitotic regulation by NIMA-related kinases. Cell Div 2007;2:25
57. Mardin BR, Schiebel E. Breaking the ties that bind: new advances in centrosome biology. J Cell Biol 2012;197(1):11-18
58. Mardin BR, Lange C, Baxter JE, et al. Components of the Hippo pathway cooperate with Nek2 kinase to regulate centrosome disjunction. Nat Cell Biol 2010;12(12):1166-76
59. Mardin BR, Agircan FG, Lange C, Schiebel E. Plk1 controls the Nek2A-PP1gamma antagonism in centrosome disjunction. Curr Biol 2011;21(13):1145-51
60. Yang J, Liu X, Yue G, et al. Rootletin, a novel coiled-coil protein, is a structural component of the ciliary rootlet. J Cell Biol 2002;159(3):431-40 (Pubitemid 35332830)
61. Fry AM, Mayor T, Meraldi P, et al. CNap1, a novel centrosomal coiled-coil protein and candidate substrate of the cell cycle-regulated protein kinase Nek2. J Cell Biol 1998;141(7):1563-74 (Pubitemid 28309171)
62. Mori D, Yano Y, Toyo-oka K, et al. NDEL1 phosphorylation by Aurora-A kinase is essential for centrosomal maturation, separation, and TACC3 recruitment. Mol Cell Biol 2007;27(1):352-67 (Pubitemid 46013256)
63. Smith E, Hegarat N, Vesely C, et al. Differential control of Eg5-dependent centrosome separation by Plk1 and Cdk1. Embo J 2011;30(11):2233-45
64. Mayer TU, Kapoor TM, Haggarty SJ, et al. Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen. Science 1999;286(5441):971-4
65. Whitehead CM, Rattner JB. Expanding the role of HsEg5 within the mitotic and post-mitotic phases of the cell cycle. J Cell Sci 1998;111(Pt 17):2551-61 (Pubitemid 28474958)
66. Kapoor TM, Mayer TU, Coughlin ML, Mitchison TJ. Probing spindle assembly mechanisms with monastrol, a small molecule inhibitor of the mitotic kinesin, Eg5. J Cell Biol 2000;150(5):975-88
67. Bertran MT, Sdelci S, Regue L, et al. Nek9 is a Plk1-activated kinase that controls early centrosome separation through Nek6/7 and Eg5. EMBO J 2011;30(13):2634-47
68. Haren L, Stearns T, Luders J. Plk1-dependent recruitment of gamma-tubulin complexes to mitotic centrosomes involves multiple PCM components. PLoS One 2009;4(6):e5976
69. Li Q, Hansen D, Killilea A, et al. Kendrin/pericentrin-B, a centrosome protein with homology to pericentrin that complexes with PCM-1. J Cell Sci 2001;114(Pt 4):797-809 (Pubitemid 32237152)
70. Heald R, Tournebize R, Habermann A, et al. Spindle assembly in Xenopus egg extracts: respective roles of centrosomes and microtubule self-organization. J Cell Biol 1997;138(3):615-28 (Pubitemid 27349842)
71. Glover DM, Leibowitz MH, McLean DA, Parry H. Mutations in aurora prevent centrosome separation leading to the formation of monopolar spindles. Cell 1995;81(1):95-105
72. Lane HA, Nigg EA. Antibody microinjection reveals an essential role for human polo-like kinase 1 (Plk1) in the functional maturation of mitotic centrosomes. J Cell Biol 1996;135(6Pt 2):1701-13 (Pubitemid 27036434)
73. Taylor S, Peters JM. Polo and Aurora kinases: lessons derived from chemical biology. Curr Opin Cell Biol 2008;20(1):77-84
74. Sen S, Zhou H, White RA. A putative serine/threonine kinase encoding gene BTAK on chromosome 20q13 is amplified and overexpressed in human breast cancer cell lines. Oncogene 1997;14(18):2195-200 (Pubitemid 27248231)
75. Zhou H, Kuang J, Zhong L, et al. Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation. Nat Genet 1998;20(2):189-93 (Pubitemid 28455454)
76. Bischoff JR, Anderson L, Zhu Y, et al. A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers. Embo J 1998;17(11):3052-65 (Pubitemid 28254378)
77. Asteriti IA, Giubettini M, Lavia P, Guarguaglini G. Aurora-A inactivation causes mitotic spindle pole fragmentation by unbalancing microtubule-generated forces. Mol Cancer 2011;10:131
78. Ring D, Hubble R, Kirschner M. Mitosis in a cell with multiple centrioles. J Cell Biol 1982;94(3):549-56 (Pubitemid 13241186)
79. Brinkley BR. Managing the centrosome numbers game: from chaos to stability in cancer cell division. Trends Cell Biol 2001;11(1):18-21 (Pubitemid 32056189)
80. Ogden A, Rida PC, Aneja R. Let's huddle to prevent a muddle: centrosome declustering as an attractive anticancer strategy. Cell Death Differ 2012;19(8):1255-67
81. Kwon M, Godinho SA, Chandhok NS, et al. Mechanisms to suppress multipolar divisions in cancer cells with extra centrosomes. Genes Dev 2008;22(16):2189-203
82. Leber B, Maier B, Fuchs F, et al. Proteins required for centrosome clustering in cancer cells. Sci Transl Med 2010;2(33):33ra38
83. Quintyne NJ, Reing JE, Hoffelder DR, et al. Spindle multipolarity is prevented by centrosomal clustering. Science 2005;307(5706):127-9 (Pubitemid 40093495)
84. Kramer A, Maier B, Bartek J. Centrosome clustering and chromosomal (in)stability: A matter of life and death. Mol Oncol 2011;5(4):324-35
85. Raab MS, Breitkreutz I, Anderhub S, et al. GF-15, a novel inhibitor of centrosomal clustering, suppresses tumor cell growth in vitro and in vivo. Cancer Res 2012; Epub ahead of print]
86. Steegmaier M, Hoffmann M, Baum A, et al. BI 2536, a potent and selective inhibitor of polo-like kinase 1, inhibits tumor growth in vivo. Curr Biol 2007;17(4):316-22 (Pubitemid 46241881)
87. Olmos D, Barker D, Sharma R, et al. Phase I study of GSK461364, a specific and competitive Polo-like kinase 1 inhibitor, in patients with advanced solid malignancies. Clin Cancer Res 2011;17(10):3420-30
88. Gumireddy K, Reddy MV, Cosenza SC, et al. ON01910, a non-ATP-competitive small molecule inhibitor of Plk1, is a potent anticancer agent. Cancer Cell 2005;7(3):275-86 (Pubitemid 40568686)
89. Garland LL, Taylor C, Pilkington DL, et al. A phase I pharmacokinetic study of HMN-214, a novel oral stilbene derivative with polo-like kinase-1-interacting properties, in patients with advanced solid tumors. Clin Cancer Res 2006;12(17):5182-9 (Pubitemid 44453347)
90. Schoffski P. Polo-like kinase (PLK) inhibitors in preclinical and early clinical development in oncology. Oncologist 2009;14(6):559-70
91. Tanaka R, Squires MS, Kimura S, et al. Activity of the multitargeted kinase inhibitor, AT9283, in imatinib-resistant BCR-ABL-positive leukemic cells. Blood 2010;116(12):2089-95
92. Dawson MA, Curry JE, Barber K, et al. AT9283, a potent inhibitor of the Aurora kinases and Jak2, has therapeutic potential in myeloproliferative disorders. Br J Haematol 2010;150(1):46-57
93. Green MR, Woolery JE, Mahadevan D. Update on aurora kinase targeted therapeutics in oncology. Expert Opin Drug Discov 2011;6(3):291-307
94. Carol H, Boehm I, Reynolds CP, et al. Efficacy and pharmacokinetic/ pharmacodynamic evaluation of the Aurora kinase A inhibitor MLN8237 against preclinical models of pediatric cancer. Cancer Chemother Pharmacol 2011;68(5):1291-304
95. Manfredi MG, Ecsedy JA, Chakravarty A, et al. Characterization of Alisertib (MLN8237), an investigational small-molecule inhibitor of aurora A kinase using novel in vivo pharmacodynamic assays. Clin Cancer Res 2011;17(24):7614-24
96. Chakravarty A, Shinde V, Tabernero J, et al. Phase I assessment of new mechanism-based pharmacodynamic biomarkers for MLN8054, a small-molecule inhibitor of Aurora A kinase. Cancer Res 2011;71(3):675-85
97. Kollareddy M, Zheleva D, Dzubak P, et al. Aurora kinase inhibitors: progress towards the clinic. Invest New Drugs 2012; Epub ahead of print
98. Hoessel R, Leclerc S, Endicott JA, et al. Indirubin, the active constituent of a Chinese antileukaemia medicine, inhibits cyclin-dependent kinases. Nat Cell Biol 1999;1(1):60-7 (Pubitemid 129495012)
99. MacCallum DE, Melville J, Frame S, et al. Seliciclib (CYC202, R-Roscovitine) induces cell death in multiple myeloma cells by inhibition of RNA polymerase II-dependent transcription and down-regulation of Mcl-1. Cancer Res 2005;65(12):5399-407 (Pubitemid 40827353)
100. Joshi KS, Rathos MJ, Mahajan P, et al. P276-00, a novel cyclin-dependent inhibitor induces G1-G2 arrest, shows antitumor activity on cisplatin-resistant cells and significant in vivo efficacy in tumor models. Mol Cancer Ther 2007;6(3):926-34 (Pubitemid 46554562)
101. Misra RN, Xiao HY, Kim KS, et al. N- (cycloalkylamino)acyl-2- aminothiazole inhibitors of cyclin-dependent kinase 2. N-[5-[[[5-(1,1- dimethylethyl)-2-oxazolyl] methyl]thio]-2-thiazolyl]-4- piperidinecarboxamide (BMS-387032), a highly efficacious and selective antitumor agent. J Med Chem 2004;47(7):1719-28 (Pubitemid 38380915)
102. Siemeister G, Lucking U, Wengner AM, et al. BAY 1000394, a novel cyclin-dependent kinase inhibitor, with potent antitumor activity in mono- and in combination treatment upon oral application. Mol Cancer Ther 2012; Epub ahead of print
103. Parry D, Guzi T, Shanahan F, et al. Dinaciclib (SCH 727965), a novel andpotent cyclin-dependent kinase inhibitor. Mol Cancer Ther 2010;9(8):2344-53
104. Brown AP, Courtney CL, Criswell KA, et al. Toxicity and toxicokinetics of the cyclin-dependent kinase inhibitor AG-024322 in cynomolgus monkeys following intravenous infusion. Cancer Chemother Pharmacol 2008;62(6):1091-101
105. Mahadevan D, Plummer R, Squires MS, et al. A phase I pharmacokinetic and pharmacodynamic study of AT7519, a cyclin-dependent kinase inhibitor in patients with refractory solid tumors. Ann Oncol 2011;22(9):2137-43
106. Senderowicz AM. Flavopiridol: The first cyclin-dependent kinase inhibitor in human clinical trials. Invest New Drugs 1999;17(3):313-20 (Pubitemid 30037961)
107. DePinto W, Chu XJ, Yin X, et al. In vitro and in vivo activity of R547: A potent and selective cyclin-dependent kinase inhibitor currently in phase I clinical trials. Mol Cancer Ther 2006;5(11):2644-58
108. Cochran JC, Gatial JE III, Kapoor TM, Gilbert SP. Monastrol inhibition of the mitotic kinesin Eg5. J Biol Chem 2005;280(13):12658-67
109. Theoclitou ME, Aquila B, Block MH, et al. Discovery of (+)-N- (3-aminopropyl)-N-[1-(5-benzyl-3- methyl-4-oxo-[1,2]thiazolo[5,4-d] pyrimidin -6-yl)-2-methylpropyl]- 4-methylbenzamide (AZD4877), a kinesin spindle protein inhibitor and potential anticancer agent. J Med Chem 2011;54(19):6734-50