Target Information
Target General Infomation | |||||
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Target ID |
T87675
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Former ID |
TTDC00006
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Target Name |
Aurora kinase A
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Gene Name |
AURKA
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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; AURKA
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Target Type |
Clinical Trial
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Disease | Acute myeloid leukemia [ICD9: 205; ICD10: C92.0] | ||||
Advanced solid tumor [ICD9: 140-199; ICD10: C00-C75, C7A, C7B] | |||||
Cancer [ICD9: 140-229; ICD10: C00-C96] | |||||
Haematological malignancies [ICD9: 200-209; ICD10: C81-C86] | |||||
Late-stage solid tumors [ICD9: 140-199, 210-229; ICD10: C00-C75, C7A, C7B, D10-D36, D3A] | |||||
Prostate cancer [ICD9: 185; ICD10: C61] | |||||
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48] | |||||
Function |
Mitotic serine/threonine kinases that contributes to the regulation of cell cycle progression. Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis. Required for initial activation of CDK1 at centrosomes. Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2. Regulates KIF2A tubulin depolymerase activity. Required for normal axon formation. Plays a role in microtubule remodeling during neurite extension. Important for microtubule formation and/or stabilization. Also acts as a key regulatory component of the p53/TP53 pathway, and particularly the checkpoint-response pathways critical for oncogenic transformation of cells, by phosphorylating and stabilizing p53/TP53. Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity. Necessary for proper cilia disassembly prior to mitosis.
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BioChemical Class |
Kinase
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Target Validation |
T87675
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UniProt ID | |||||
EC Number |
EC 2.7.11.1
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Sequence |
MDRSKENCISGPVKATAPVGGPKRVLVTQQFPCQNPLPVNSGQAQRVLCPSNSSQRVPLQ
AQKLVSSHKPVQNQKQKQLQATSVPHPVSRPLNNTQKSKQPLPSAPENNPEEELASKQKN EESKKRQWALEDFEIGRPLGKGKFGNVYLAREKQSKFILALKVLFKAQLEKAGVEHQLRR EVEIQSHLRHPNILRLYGYFHDATRVYLILEYAPLGTVYRELQKLSKFDEQRTATYITEL ANALSYCHSKRVIHRDIKPENLLLGSAGELKIADFGWSVHAPSSRRTTLCGTLDYLPPEM IEGRMHDEKVDLWSLGVLCYEFLVGKPPFEANTYQETYKRISRVEFTFPDFVTEGARDLI SRLLKHNPSQRPMLREVLEHPWITANSSKPSNCQNKESASKQS |
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Drugs and Mode of Action | |||||
Drug(s) | AT9283 | Drug Info | Phase 3 | Solid tumours | [533017], [542864] |
MLN8237 | Drug Info | Phase 3 | Cancer | [523707], [542741] | |
ENMD-2076 | Drug Info | Phase 2 | Acute myeloid leukemia | [531311], [542810] | |
PHA-739358 | Drug Info | Phase 2 | Prostate cancer | [542852], [548410] | |
VX-680 | Drug Info | Phase 2 | Solid tumours | [526974], [541056] | |
AMG 900 | Drug Info | Phase 1 | Solid tumours | [531205], [542948] | |
CYC116 | Drug Info | Phase 1 | Solid tumours | [522163] | |
MK-5108 | Drug Info | Phase 1 | Cancer | [542949], [548558] | |
MLN8054 | Drug Info | Phase 1 | Solid tumours | [522281], [541037] | |
R763 | Drug Info | Phase 1 | Haematological malignancies | [549926] | |
SNS-314 | Drug Info | Phase 1 | Solid tumours | [522092] | |
SU-6668 | Drug Info | Phase 1 | Advanced solid tumor | [527156], [542760] | |
TAS-119 | Drug Info | Phase 1 | Late-stage solid tumors | [549555] | |
PF-03814735 | Drug Info | Discontinued in Phase 1 | Advanced solid tumor | [548451] | |
Inhibitor | 2-(1H-pyrazol-3-yl)-1H-benzimidazole | Drug Info | [551374] | ||
4-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine | Drug Info | [530806] | |||
6-bromoindirubin-3-oxime | Drug Info | [528968] | |||
7-fluoroindirubin-3-oxime | Drug Info | [528968] | |||
Adenosine-5'-Diphosphate | Drug Info | [551391] | |||
CYC116 | Drug Info | [550374] | |||
ENMD-2076 | Drug Info | [537564] | |||
Indirubin-3-acetoxime | Drug Info | [528968] | |||
Indirubin-3-methoxime | Drug Info | [528968] | |||
Indirubin-3-oxime | Drug Info | [528968] | |||
MK-5108 | Drug Info | [549718], [550064] | |||
MLN8054 | Drug Info | [536401], [536474], [551717] | |||
MLN8237 | Drug Info | [549980] | |||
PF-03814735 | Drug Info | [537564] | |||
PHA-739358 | Drug Info | [537564] | |||
Phosphonothreonine | Drug Info | [551393] | |||
R763 | Drug Info | [537610] | |||
SNS-314 | Drug Info | [537044], [537212], [537234], [537635] | |||
SU-6668 | Drug Info | [536137], [536474] | |||
TAS-119 | Drug Info | [549967] | |||
VX-680 | Drug Info | [536474], [537553] | |||
ZM-447439 | Drug Info | [528348] | |||
Modulator | AMG 900 | Drug Info | [531205] | ||
AT9283 | Drug Info | [533017] | |||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
TEP | EXP Info | ||||
Pathways | |||||
KEGG Pathway | Oocyte meiosis | ||||
Pathway Interaction Database | Aurora B signaling | ||||
Signaling by Aurora kinases | |||||
Integrin-linked kinase signaling | |||||
PLK1 signaling events | |||||
Aurora A signaling | |||||
Reactome | Cdh1 targeted proteins in late mitosis/early G1 | ||||
Regulation of PLK1 Activity at G2/M Transition | |||||
WikiPathways | EGF/EGFR Signaling Pathway | ||||
JAK/STAT | |||||
Gastric Cancer Network 1 | |||||
Integrated Breast Cancer Pathway | |||||
APC/C-mediated degradation of cell cycle proteins | |||||
References | |||||
Ref 522092 | ClinicalTrials.gov (NCT00519662) Safety and Tolerability Study of SNS-314 for Advanced Solid Tumors. U.S. National Institutes of Health. | ||||
Ref 522163 | ClinicalTrials.gov (NCT00560716) A Phase I Pharmacologic Study of CYC116, an Oral Aurora Kinase Inhibitor, in Patients With Advanced Solid Tumors. U.S. National Institutes of Health. | ||||
Ref 522281 | ClinicalTrials.gov (NCT00652158) A Phase 1 Trial of Extended MLN8054 Dosing in Patients With Advanced Malignancies. U.S. National Institutes of Health. | ||||
Ref 523707 | ClinicalTrials.gov (NCT01482962) Alisertib (MLN8237) or Investigator's Choice in Patients With Relapsed/Refractory Peripheral T-Cell Lymphoma. U.S. National Institutes of Health. | ||||
Ref 526974 | Nat Med. 2004 Mar;10(3):262-7. Epub 2004 Feb 22.VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. | ||||
Ref 527156 | A phase I surrogate endpoint study of SU6668 in patients with solid tumors. Invest New Drugs. 2004 Nov;22(4):459-66. | ||||
Ref 531205 | Preclinical evaluation of AMG 900, a novel potent and highly selective pan-aurora kinase inhibitor with activity in taxane-resistant tumor cell lines. Cancer Res. 2010 Dec 1;70(23):9846-54. | ||||
Ref 531311 | ENMD-2076 is an orally active kinase inhibitor with antiangiogenic and antiproliferative mechanisms of action. Mol Cancer Ther. 2011 Jan;10(1):126-37. | ||||
Ref 533017 | A phase I trial of AT9283 (a selective inhibitor of aurora kinases) in children and adolescents with solid tumors: a Cancer Research UK study. Clin Cancer Res. 2015 Jan 15;21(2):267-73. | ||||
Ref 541037 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5696). | ||||
Ref 541056 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5718). | ||||
Ref 542741 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7790). | ||||
Ref 542760 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7816). | ||||
Ref 542810 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7885). | ||||
Ref 542852 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7937). | ||||
Ref 542864 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7949). | ||||
Ref 542948 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8060). | ||||
Ref 542949 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8061). | ||||
Ref 548410 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025382) | ||||
Ref 548451 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025628) | ||||
Ref 548558 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026594) | ||||
Ref 528348 | 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. | ||||
Ref 528968 | 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. | ||||
Ref 530806 | 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. | ||||
Ref 531205 | Preclinical evaluation of AMG 900, a novel potent and highly selective pan-aurora kinase inhibitor with activity in taxane-resistant tumor cell lines. Cancer Res. 2010 Dec 1;70(23):9846-54. | ||||
Ref 533017 | A phase I trial of AT9283 (a selective inhibitor of aurora kinases) in children and adolescents with solid tumors: a Cancer Research UK study. Clin Cancer Res. 2015 Jan 15;21(2):267-73. | ||||
Ref 536137 | 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. | ||||
Ref 536401 | 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. | ||||
Ref 536474 | 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. | ||||
Ref 537044 | Water-soluble prodrugs of an Aurora kinase inhibitor. Bioorg Med Chem Lett. 2009 Mar 1;19(5):1409-12. Epub 2009 Jan 19. | ||||
Ref 537234 | 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. | ||||
Ref 537553 | Essential roles of mTOR/Akt pathway in Aurora-A cell transformation. Int J Biol Sci. 2009 Jun 19;5(5):444-50. | ||||
Ref 537564 | Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66. | ||||
Ref 537610 | Preclinical characterization of Aurora kinase inhibitor R763/AS703569 identified through an image-based phenotypic screen. J Cancer Res Clin Oncol. 2009 Jul 17. | ||||
Ref 537635 | SNS-314, a pan-Aurora kinase inhibitor, shows potent anti-tumor activity and dosing flexibility in vivo. Cancer Chemother Pharmacol. 2009 Aug 1. | ||||
Ref 549718 | A novel c-Met inhibitor, MK8033, synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth. Oncol Rep. 2013 May;29(5):2011-8. | ||||
Ref 549967 | TAS-119, a selective Aurora A inhibitor, enhanced the antitumor efficacy of taxanes in multiple human tumor cell lines including paclitaxel-resistant cells. Molecular Cancer Therapeutics. 01/2014; 12(11_Supplement):A268-A268. | ||||
Ref 549980 | 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. | ||||
Ref 550064 | Anticancer activity of the Aurora A kinase inhibitor MK-5108 in non-small-cell lung cancer (NSCLC) in vitro as monotherapy and in combination with chemotherapies. J Cancer Res Clin Oncol. 2014 Jul;140(7):1137-49. |
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