ced hematological malignancies. BMS-754807 BMS754807 Blood . 2008, 112 abstr 2963. 150. Mahadevan D, Qi W, Cooke L, et al. Targeting aurora kinase in aggressive B cell non Hodgkin,s lymphomas. Blood . 2009, 114 abstr 284. 151. den Hollander J, Rimpi S, Doherty JR, et al. Aurora kinases A and B are up regulated by Myc and are essential for maintenance of the malignant state. Blood. 2010, 116:1498 505. 152. Yang D, Liu H, Goga A, et al. Therapeutic potential of a synthetic lethal interaction between the MYC proto oncogene and inhibition of aurora B kinase. Proc Natl Acad Sci U S A. 2010, 107:13836 41. Green et al. Page 22 Expert Opin Drug Discov. Author manuscript, available in PMC 2012 March 1. NIH PA Author Manuscript NIH PA Author Manuscript NIH PA Author Manuscript Figure 1.
Sensitizing Cancer Cells to SAC inhibition plus microtubule targeting agents to optimize enhanced Apoptosis Green et al. Page 23 Expert Opin Drug Discov. Author manuscript, available in PMC 2012 March 1. NIH PA Author Manuscript NIH PA Author Manuscript NIH PA Author Manuscript NIH PA Author Manuscript NIH PA Author Manuscript NIH PA Author Manuscript Green et al. Page 24 Table 1 IC50 for JNJ-38877605 selected Aurora kinase inhibitors IC50 values in nM Aurora A kinase Aurora B kinase Aurora C kinase Reference ENMD 981693 25 700 NA 23 ENMD 2076 14 350 NA 24 MK 5108/VX 689 0.064 14 12 29 MLN 8054 4 172 NA 32 MLN 8237 1 >200 NA 44 XL 228 3 NA NA 52 KW 2449 48 NA NA 55 Hesperadin NA 50 NA 10 BI 811283 NA 9 NA 57 AZD 1152 1369 0.36 17 20 GSK 1070916 490 0.38 1.5 81 ZM 447439 100 100 NA 77 JNJ 7706621 11 15 NA 89 AT 9283 3 3 NA 90 PF 03814735 5 0.
8 NA 101 VX 680/MK 0457 0.7 18 4.6 10 PHA 680632 27 135 120 64 PHA 739358 13 79 61 125 CYC 116 44 19 65 131 SNS 314 9 31 3.4 136 AMG 900 5 4 1 139 VE 465 1 26 8.7 142 AS 703569 4 4.8 6.8 145 NA = Not available Expert Opin Drug Discov. Author manuscript, available in PMC 2012 March 1. NIH PA Author Manuscript NIH PA Author Manuscript NIH PA Author Manuscript Green et al.
Page 25 Table 2 Evidence of clinical activity of Aurora kinase inhibitors by malignancy and study design* Breast Bladder Head and Neck Lung Prostate Renal Cell Colorectal Pancreatic Hepatocellular Melanoma Glioma Ovarian Endometroid Carcinoma Cervix Acute Myelogenous Leukemia Chronic Myelogenous Leukemia Acute Lymphoblastic Leukemia Multiple Myeloma Lymphomas Mantle Cell Lymphoma Myeloproliferative Disorders ENMD 981693 1 1 1 1 1 ENMD 2076 1,2 1,4 1 4 1 1,2 MK 5108/VX 689 1 1 1 1 1,2 1 1 MLN 8054 1,6 6 6 1,6 1 1,6 6 6 6 1,6 1 MLN 8237 1,2 4 1,4 2 1,4 4 1,2 1,2 1 1 1,2 1,2 XL 228 4 1,4 1,4 KW 2449 1,4 1,4 1 BI 811283 1 1 AZD 1152 1 1 1,2 1 1 1 1 1,2 1 1,2 1 1,2 GSK 1070916 1,3 1 1 1 1 ZM 447439 1 1 1 1 1 JNJ 7706621 1 1 1 1 1 1 AT 9283 1 1,4,6 1,6 1 1 1,4 1,4 1 1 PF 03814735 1,6 6 6 1,6 6 1,6 6 1 1 VX 680/MK 0457 1,2 6 2,6 1,2,6 1,6 1,6 1,6 1,2,6 1,2,4 1,2,4,5 1,2,4,5 1 1,2 1,4 PHA 680632 1 1 1 1 1 1 PHA 739358 1,5,6,7 1,4 1,6 1,6 1,5,6 6,7 1 1,5,6,7 1 1 1,2,4 1,4 CYC 116 1 1 1 1 SNS 314 1 1 1 1,2 AMG 900 1 1 1 1 1 1 1 1 1 1 1 1 1 VE 465 1,2 1 1 1,2 1,2 1,2 1,2 AS 703569/R 763 1 1 1 1 1 1 1 1,4 1,4 1 1 1 Single drug efficacy, Preclinical�? 2 Combination efficacy, Preclinical�? Expert Opin Drug Discov.
Author manuscript, available in PMC 2012 March 1. NIH PA Author Manuscript NIH PA Author Manuscript NIH PA Author Manuscript Green et al. Page 26 3 No/minimal efficacy, Preclinical�? 4 Single drug efficacy, Phase I�? 5 Combination efficacy, Phase I�? 6 No/minimal efficacy, Phase I�? 7 Single drug efficacy, Phase II�?* Where data available/reported, �?Defined as objective response or partial/complete response, �?Defined as stable disease or no objective response Expert Opin Drug Discov. Author manuscript, available in PMC 2012 March 1. Enhanced Radiosensitivity of Androgen Resistant Prostate Cancer: AZD1152 Mediated Aurora Kinase B Inhibition Kenneth J. Niermann, Luigi Moretti, Nicholas J. Giacalone, Yunguang Sun, Stephen M. Schleicher, Prapaporn Kopsombut, Lauren R. Mitchell, Kwang