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2010, 107 :13836�?1. 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 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-038