TTD Target ID: TTDC00006

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

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