Estrogen Receptor with a selective target inhibition profile relevant to cancer.

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Cancer Res 2005,65:9038�?6. 66. Seamon JA, Rugg CA, Emanuel S, et al. Role of the ABCG2 drug transporter in the resistance and oral bioavailability of a potent cyclin dependent kinase/Aurora kinase inhibitor. Mubritinib Mol Cancer Ther 2006,5:2459�?7. 67. Laird AD, Vajkoczy P, Shawver LK, et al. SU6668 is a potent antiangiogenic and antitumor agent that induces regression of established tumors. Cancer Res 2000,60:4152�?0. 68. Godl K, Gruss OJ, Eickhoff J, et al. Proteomic characterization of the angiogenesis inhibitor SU6668 reveals multiple impacts on cellular kinase signaling. Cancer Res 2005,65:6919�?6. 69. Chan F, Sun C, Perumal M, et al. Mechanism of action of the Aurora kinase inhibitor CCT129202 and in vivo quantification of biological activity.
Mol Cancer Ther 2007,6:3147�?7. 70. Barthel H, Perumal M, Latigo J, et al. The uptake of 3, deoxy 3, fluorothymidine into L5178Y tumours in vivo is dependent on thymidine kinase 1 protein levels. Eur J Nucl Med Mol Imaging 2005,32:257�?3. 71. Kristeleit R, Calvert H, Arkenau H, et al. A phase I study of AT9283, an aurora kinase inhibitor, in patients with refractory solid tumors. J Clin Oncol 2009,27:2566. 72. Arbitrario JP, Belmont BJ, Evanchik MJ, et al. SNS 314, a pan Aurora kinase inhibitor, shows potent anti tumor activity and dosing flexibility in vivo. Cancer Chemother Pharmacol. 2009 73. Griffiths G, Scaerou F, Midgley C, et al. Anti tumor activity of CYC116, a novel small molecule inhibitor of Aurora kinases and VEGFR2. AACR Meeting Abstracts 2008:5644. 74.
Jones SF, Burris HA III, Dumez H, et al. Phase I accelerated dose escalation, pharmacokinetic and pharmacodynamic study of PF 03814735, an oral aurora kinase inhibitor, in patients with advanced solid tumors: Preliminary results. Journal of Clinical Oncolgy 2008,26:2517. Dar et al. Page 14 Mol Cancer Ther. Author manuscript, available in PMC 2011 February 2. NIH PA Author Manuscript NIH PA Author Manuscript NIH PA Author Manuscript 75. Yang H, He L, Kruk P, Nicosia SV, Cheng JQ. Aurora A induces cell survival and chemoresistance by activation of Akt through a p53 dependent manner in ovarian cancer cells. Int J Cancer 2006,119:2304�?2. Dar et al. Page 15 Mol Cancer Ther. Author manuscript, available in PMC 2011 February 2. NIH PA Author Manuscript NIH PA Author Manuscript NIH PA Author Manuscript Figure 1.
Schematic diagram of Aurora A, B, & C kinase domains. N & C terminal domains contain most of the regulatory sequences. The central domain consists of catalytic kinase domain and activation loop. D Box at the c terminal domain is the destruction box. Brown box Activation loop, Black box destruction box at C terminus, Light green box destruction box at N terminus, Light green box Kinase domain. Dar et al. Page 16 Mol Cancer Ther. Author manuscript, available in PMC 2011 February 2. NIH PA Author Manuscript NIH PA Author Manuscript NIH PA Author Manuscript Figure 2. Overvie

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