Target
Information |
Name | Aurora kinase A |
Type of target | Clinical trial target |
Synonyms | Aurora-A |
Aurora-related kinase 1 |
Aurora/IPL1-related kinase 1 |
Breast tumor-amplified kinase |
Serine/threonine kinase 15 |
Serine/threonine-protein kinase 6 |
hARK1 |
Disease | Colorectal Cancer [1][2] |
Lymphoma, Unspecified [3][4][5] |
Solid tumors [6][7][8] |
Drug(s) | AZD1152 |  | Phase II | Acute Myeloid Leukemia, Haematological malignancies | [9] |
ENMD-2076 |  | Phase II | Ovarian Cancer, Fallopian Cancer, Peritoneal Cancer | [10] |
MLN8237 |  | Phase II | Acute myelogenous leukemia, High-risk myelodysplastic syndrome and Ovarian cancer | [11] |
PHA-739358 |  | Phase II | CML that relapsed after imatinib or BCR¨CABL-targeted therapy; Metastatic Hormone Refractory Prostate Cancer (MHRPC) | [10] |
AT-9283 |  | Phase I/II | Adult solid tumours, NHL, AML, ALL, CML, MDS and myelofibrosis | [10] |
AZD1152 |  | Phase I/II | Myeloid Leukemia | [9] |
MLN8237 |  | Phase I/II | Paediatric solid tumours or ALL | [11] |
SNS-314 |  | Phase I completed | Solid Tumors | [12][6][7][8][12] |
AT9283 |  | Phase I | Leukemia, Myeloid | [13][14] |
MK-5108 |  | Phase I | Cancer; Neoplasms; Tumors | [15][16] |
MLN8237 |  | Phase I | Advanced solid tumours and haematological malignancies | [11] |
PF-03814735 |  | Phase I | Advanced solid tumours | [10] |
R763 |  | Phase I | Haematological Malignancies | [17] |
VX-689 |  | Phase I | Cancer; Neoplasms; Tumors | [10] |
CYC-116 |  | Terminated in Phase I | Advanced solid tumours | [10] |
CYC116 |  | Terminated in Phase I | Solid Tumors | [18] |
MLN8054 |  | Terminated in Phase I | Solid tumours | [19][20][21] |
MLN8054 |  | Terminated in Phase I | Advanced malignancies | [19][20][21] |
SU-6668 |  | Discontinued | Advanced solid tumours | [19][22] |
VX-680 |  | Terminated in Phase II | Leukemia | [19][1] |
VX-680 |  | Terminated in Phase I | Chronic Myelogenous Leukemia; Leukemia; Lymphoblastic, Acute, Philadelphia-Positive | [19][1] |
EC Number | EC 2.7.11.1 |
UniProt ID | O14965 |
PDB Structure | 1MQ4; 1MUO; 1OL5; 1OL6; 1OL7; 2BMC; 2C6D; 2C6E. |
Sequence | MDRSKENCISGPVKATAPVGGPKRVLVTQQFPCQNPLPVNSGQAQRVLCPSNSSQRVPLQ
AQKLVSSHKPVQNQKQKQLQATSVPHPVSRPLNNTQKSKQPLPSAPENNPEEELASKQKN
EESKKRQWALEDFEIGRPLGKGKFGNVYLAREKQSKFILALKVLFKAQLEKAGVEHQLRR
EVEIQSHLRHPNILRLYGYFHDATRVYLILEYAPLGTVYRELQKLSKFDEQRTATYITEL
ANALSYCHSKRVIHRDIKPENLLLGSAGELKIADFGWSVHAPSSRRTTLCGTLDYLPPEM
IEGRMHDEKVDLWSLGVLCYEFLVGKPPFEANTYQETYKRISRVEFTFPDFVTEGARDLI
SRLLKHNPSQRPMLREVLEHPWITANSSKPSNCQNKESASKQS
|
Target Validation | Click to Find Target Validation Information. |
Inhibitor | 2- (1H-pyrazol-3-yl)-1H-benzimidazole |  | [23] |
4- (1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine |  | [24] |
6-bromoindirubin-3-oxime |  | [25] |
7-fluoroindirubin-3-oxime |  | [25] |
AT-9283 |  | [10] |
AT9283 |  | [13][14] |
AZD-1152-HQPA, Barasertib |  | [26] |
AZD1152 |  | [9] |
Adenosine-5'-Diphosphate |  | [27] |
CYC-116 |  | [10] |
CYC116 |  | [18] |
ENMD-2076 |  | [10] |
GSK-1070916 |  | [28] |
MK-5108 |  | [15][16] |
MLN8054 |  | [19][20][21] |
MLN8237 |  | [11] |
PF-03814735 |  | [10] |
PHA-680632 |  | [29] |
PHA-739358 |  | [10] |
Phosphonothreonine |  | [30] |
R763 |  | [17] |
SNS-314 |  | [12][6][7][8][12] |
SU-6668 |  | [19][22] |
VX-680 |  | [19][1] |
VX-689 |  | [10] |
ZM-447439 |  | [31] |
indirubin-3-acetoxime |  | [25] |
indirubin-3-methoxime |  | [25] |
indirubin-3-oxime |  | [25] |
Multitarget | AT-9283 |  | [10] |
AT9283 |  | [13][14] |
AZD1152 |  | [9] |
CYC-116 |  | [10] |
CYC116 |  | [18] |
MK-5108 |  | [15][16] |
PF-03814735 |  | [10] |
PHA-739358 |  | [10] |
R763 |  | [17] |
SNS-314 |  | [12][6][7][8][12] |
SU-6668 |  | [19][22] |
VX-680 |  | [19][1] |
VX-689 |  | [10] |
Cross References |
3D Structure
Related Literature
On-Line
Medical Dictionary |
Ref 1 | Essential roles of mTOR/Akt pathway in Aurora-A cell transformation. Int J Biol Sci. 2009 Jun 19;5(5):444-50. To Reference |
Ref 2 | Research Progress on Aurora Kinase Inhibitor MK-0457 in Therapy for Some Hematological Malignancies-Review.. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2009 Jun;17(3):810-5. To Reference |
Ref 3 | Determinants for the efficiency of anticancer drugs targeting either Aurora-A or Aurora-B kinases in human colon carcinoma cells. Mol Cancer Ther. 2009 Jul;8(7):2046-56. Epub 2009 Jul 7. To Reference |
Ref 4 | Discovery and exploitation of inhibitor-resistant aurora and polo kinase mutants for the analysis of mitotic networks. J Biol Chem. 2009 Jun 5;284(23):15880-93. Epub 2009 Apr 9. To Reference |
Ref 5 | The inhibition of Aurora A abrogates the mitotic delay induced by microtubule perturbing agents. Cell Cycle. 2009 Mar 15;8(6):876-88. Epub 2009 Mar 21. To Reference |
Ref 6 | The Aurora kinase inhibitor SNS-314 shows broad therapeutic potential with chemotherapeutics and synergy with microtubule-targeted agents in a colon carcinoma model. Mol Cancer Ther. 2009 Apr;8(4):930-9. To Reference |
Ref 7 | Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2009 Jan-Feb;31(1):47-57. To Reference |
Ref 8 | Water-soluble prodrugs of an Aurora kinase inhibitor. Bioorg Med Chem Lett. 2009 Mar 1;19(5):1409-12. Epub 2009 Jan 19. To Reference |
Ref 9 | AstraZeneca. Product Development Pipeline. January 29 2009. To Reference |
Ref 10 | Nat Rev Drug Discov. 2009 Jul;8(7):547-66.Cell cycle kinases as therapeutic targets for cancer. To Reference |
Ref 11 | Effect of Aurora A kinase inhibitor MLN8237 combined with rituximab on antitumor activity in preclinical B-cell non-Hodgkin's lymphoma models. Journal of Clinical Oncology, 2009:8553 To Reference |
Ref 12 | SNS-314, a pan-Aurora kinase inhibitor, shows potent anti-tumor activity and dosing flexibility in vivo. Cancer Chemother Pharmacol. 2009 Aug 1. [Epub ahead of print] To Reference |
Ref 13 | Aurora B kinase inhibition in mitosis: strategies for optimising the use of aurora kinase inhibitors such as AT9283. Cell Cycle. 2009 Jun 15;8(12):1921-9. Epub 2009 Jun 15. To Reference |
Ref 14 | J Med Chem. 2009 Jan 22;52(2):379-88.Fragment-based discovery of the pyrazol-4-yl urea (AT9283), a multitargeted kinase inhibitor with potent aurora kinase activity. To Reference |
Ref 15 | Merck. Product Development Pipeline. July 15 2009. To Reference |
Ref 16 | Merck. Report of Merck. 2009. To Reference |
Ref 17 | J Cancer Res Clin Oncol. 2010 Jan;136(1):99-113.Preclinical characterization of Aurora kinase inhibitor R763/AS703569 identified through an image-based phenotypic screen. To Reference |
Ref 18 | Report from Cyclacel Pharmaceuticals. Cyclacel Limited. April 2008 To Reference |
Ref 19 | A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22. To Reference |
Ref 20 | Takeda. Product Development Pipeline. July 31 2009. To Reference |
Ref 21 | MLN8054, a small-molecule inhibitor of Aurora A, causes spindle pole and chromosome congression defects leading to aneuploidy. Mol Cell Biol. 2007 Jun;27(12):4513-25. Epub 2007 Apr 16. To Reference |
Ref 22 | Dose-finding study of the multitargeted tyrosine kinase inhibitor SU6668 in patients with advanced malignancies. Clin Cancer Res. 2005 Sep 1;11(17):6240-6. To Reference |
Ref 23 | Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. To Reference |
Ref 24 | Bioorg Med Chem Lett. 2010 Apr 15;20(8):2552-5. Epub 2010 Mar 1.Discovery of a new series of Aurora inhibitors through truncation of GSK1070916. To Reference |
Ref 25 | J Med Chem. 2007 Aug 23;50(17):4027-37. Epub 2007 Aug 1.An integrated computational approach to the phenomenon of potent and selective inhibition of aurora kinases B and C by a series of 7-substituted indirubins. To Reference |
Ref 26 | J Med Chem. 2007 May 3;50(9):2213-24. Epub 2007 Mar 21.Discovery, synthesis, and in vivo activity of a new class of pyrazoloquinazolines as selective inhibitors of aurora B kinase. To Reference |
Ref 27 | Nucleic Acids Res. 2011 January; 39(Database issue): D1035¨CD1041. DrugBank 3.0: a comprehensive resource for ¡®Omics¡¯ research on drugs To Reference |
Ref 28 | J Med Chem. 2010 May 27;53(10):3973-4001.Discovery of GSK1070916, a potent and selective inhibitor of Aurora B/C kinase. To Reference |
Ref 29 | J Med Chem. 2005 Apr 21;48(8):3080-4.Potent and selective Aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition. To Reference |
Ref 30 | Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. To Reference |
Ref 31 | J Med Chem. 2006 Aug 10;49(16):4805-8.Accurate prediction of the relative potencies of members of a series of kinase inhibitors using molecular docking and MM-GBSA scoring. To Reference |