Target Information

Target General Infomation
Target ID
T97592
Former ID
TTDC00059
Target Name
Aurora protein kinase
Gene Name
AURKC
Synonyms
Aurora-C; Aurora/Ipl1-related kinase 3; Aurora/Ipl1/Eg2 protein 2; AURKC
Target Type
Clinical Trial
Disease Advanced solid tumor [ICD9: 140-199; ICD10: C00-C75, C7A, C7B]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Hematological malignancies [ICD9: 200-209; ICD10: C81-C86]
Leukemia [ICD9: 208.9; ICD10: C90-C95]
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 ofCDK1 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.
BioChemical Class
Kinase
Target Validation
T91188
UniProt ID
Q9UQB9
EC Number
EC 2.7.11.1
Sequence
MSSPRAVVQLGKAQPAGEELATANQTAQQPSSPAMRRLTVDDFEIGRPLGKGKFGNVYLA
RLKESHFIVALKVLFKSQIEKEGLEHQLRREIEIQAHLQHPNILRLYNYFHDARRVYLIL
EYAPRGELYKELQKSEKLDEQRTATIIEELADALTYCHDKKVIHRDIKPENLLLGFRGEV
KIADFGWSVHTPSLRRKTMCGTLDYLPPEMIEGRTYDEKVDLWCIGVLCYELLVGYPPFE
SASHSETYRRILKVDVRFPLSMPLGARDLISRLLRYQPLERLPLAQILKHPWVQAHSRRV
LPPCAQMAS
Structure
1MQ4; 1MUO; 1OL5; 1OL6; 1OL7; 2BMC; 2C6D; 2C6E; 2DWB; 2J4Z; 2J50; 2NP8; 2W1C; 2W1D; 2W1E; 2W1F; 2W1G; 2WQE; 2WTV; 2WTW; 2X6D; 2X6E; 2X81; 2XNE; 2XNG; 2XRU; 3COH; 3E5A; 3EFW; 3FDN; 3H0Y; 3H0Z; 3H10; 3HA6; 3K5U; 3LAU; 3M11; 3MYG; 3NRM; 3O50; 3O51; 3P9J; 3QBN; 3R21; 3R22; 3UNZ; 3UO4; 3UO5; 3UO6; 3UOD; 3UOH; 3UOJ; 3UOK; 3UOL; 3UP2; 3UP7; 3VAP; 3W10; 3W16; 3W18; 3W2C; 4B0G; 4BN1; 4BYI; 4BYJ; 4C3P; 4C3R; 4DEA; 4DEB; 4DED; 4DEE; 4DHF; 4J8M; 4J8N; 4JAI; 4JAJ; 4JBO; 4JBP; 4JBQ; 4O0S; 4O0U; 4O0W; 4PRJ; 4UYN; 4UZD; 4UZH
Drugs and Mode of Action
Drug(s) Radotinib Drug Info Phase 3 Leukemia [523761], [542758]
ABT-348 Drug Info Phase 2 Hematological malignancies [525239]
PHA-739358 Drug Info Phase 2 Prostate cancer [542852], [548410]
AMG 900 Drug Info Phase 1 Solid tumours [531205], [542948]
GSK1070916 Drug Info Phase 1 Advanced solid tumor [543084], [549088]
GSK1070916A Drug Info Phase 1 Solid tumours [523030]
HPP-607 Drug Info Phase 1 Cancer [522723]
SNS-314 Drug Info Phase 1 Solid tumours [522092]
MK-6592 Drug Info Discontinued in Phase 1 Cancer [548341]
Inhibitor 2np8 Drug Info [528573]
6-bromoindirubin-3-oxime Drug Info [528968]
7-bromoindirubin-3-acetoxime Drug Info [528968]
7-bromoindirubin-3-oxime Drug Info [528968]
7-chloroindirubin-3-oxime Drug Info [528968]
7-fluoroindirubin-3-acetoxime Drug Info [528968]
7-fluoroindirubin-3-oxime Drug Info [528968]
7-iodoindirubin-3-oxime Drug Info [528968]
BMS-739562 Drug Info [543524]
BPR1K-0224 Drug Info [543524]
compound 10 Drug Info [530097]
compound 16 Drug Info [529760]
compound 25 Drug Info [531168]
compound 46 Drug Info [528000]
Glycyl-H 1152 Drug Info [527785]
HPP-607 Drug Info [543524]
Indirubin-3-acetoxime Drug Info [528968]
Indirubin-3-methoxime Drug Info [528968]
Indirubin-3-oxime Drug Info [528968]
K00244 Drug Info [530144]
MK-6592 Drug Info [530317]
MP-529 Drug Info [543524]
PHA-739358 Drug Info [527513]
quinazoline deriv. 1 Drug Info [529213]
SNS-314 Drug Info [537044], [537212], [537234], [537635]
SNS-314 prodrugs Drug Info [543524]
SU 6656 Drug Info [529039]
Modulator ABT-348 Drug Info [532023]
AMG 900 Drug Info [531205]
GSK1070916 Drug Info [530869]
GSK1070916A Drug Info [525366], [530869]
Radotinib Drug Info
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Oocyte meiosis
Reactome Cdh1 targeted proteins in late mitosis/early G1
Separation of Sister Chromatids
Resolution of Sister Chromatid Cohesion
RHO GTPases Activate Formins
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 522092ClinicalTrials.gov (NCT00519662) Safety and Tolerability Study of SNS-314 for Advanced Solid Tumors. U.S. National Institutes of Health.
Ref 522723ClinicalTrials.gov (NCT00939172) TTP607 in Refractory Solid Malignancies. U.S. National Institutes of Health.
Ref 523030ClinicalTrials.gov (NCT01118611) Aurora B/C Kinase Inhibitor GSK1070916A in Treating Patients With Advanced Solid Tumors. U.S. National Institutes of Health.
Ref 523761ClinicalTrials.gov (NCT01511289) Radotinib Versus Imatinib in Newly Diagnosed Philadelphia Chromosome and Chronic Myeloid Leukemia Chronic Phase Patients. U.S. National Institutes of Health.
Ref 525239ClinicalTrials.gov (NCT02478320) Phase II Study of Ilorasertib (ABT348) in Patients With CDKN2A Deficient Solid Tumors.
Ref 531205Preclinical 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 542758(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: 7814).
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 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 543084(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: 8358).
Ref 548341Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024789)
Ref 548410Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025382)
Ref 549088Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032133)
Ref 525366GSK1070916, a potent Aurora B/C kinase inhibitor with broad antitumor activity in tissue culture cells and human tumor xenograft models. Mol Cancer Ther. 2009 Jul;8(7):1808-17.
Ref 527513J 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.
Ref 527785Development of specific Rho-kinase inhibitors and their clinical application. Biochim Biophys Acta. 2005 Dec 30;1754(1-2):245-52. Epub 2005 Sep 12.
Ref 528000J Med Chem. 2006 Feb 9;49(3):955-70.Discovery of novel and potent thiazoloquinazolines as selective Aurora A and B kinase inhibitors.
Ref 528573Structural basis for the inhibition of Aurora A kinase by a novel class of high affinity disubstituted pyrimidine inhibitors. Bioorg Med Chem Lett. 2007 Feb 1;17(3):688-91. Epub 2006 Nov 2.
Ref 528968J 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 529039Biochem J. 2007 Dec 15;408(3):297-315.The selectivity of protein kinase inhibitors: a further update.
Ref 529213Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8. Epub 2007 Dec 11.A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases.
Ref 529760Pyrrolo-pyrimidones: a novel class of MK2 inhibitors with potent cellular activity. Bioorg Med Chem Lett. 2008 Dec 1;18(23):6142-6.
Ref 530097A class of 2,4-bisanilinopyrimidine Aurora A inhibitors with unusually high selectivity against Aurora B. J Med Chem. 2009 May 28;52(10):3300-7.
Ref 530144The discovery of the potent aurora inhibitor MK-0457 (VX-680). Bioorg Med Chem Lett. 2009 Jul 1;19(13):3586-92.
Ref 530317Clinical experience with aurora kinase inhibitors: a review. Oncologist. 2009 Aug;14(8):780-93.
Ref 530869J Med Chem. 2010 May 27;53(10):3973-4001.Discovery of GSK1070916, a potent and selective inhibitor of Aurora B/C kinase.
Ref 531168Discovery of orally bioavailable imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors. Bioorg Med Chem Lett. 2010 Nov 15;20(22):6739-43.
Ref 531205Preclinical 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 532023Preclinical characterization of ABT-348, a kinase inhibitor targeting the aurora, vascular endothelial growth factor receptor/platelet-derived growth factor receptor, and Src kinase families. J Pharmacol Exp Ther. 2012 Dec;343(3):617-27.
Ref 537044Water-soluble prodrugs of an Aurora kinase inhibitor. Bioorg Med Chem Lett. 2009 Mar 1;19(5):1409-12. Epub 2009 Jan 19.
Ref 537212Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2009 Jan-Feb;31(1):47-57.
Ref 537234The 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 537635SNS-314, a pan-Aurora kinase inhibitor, shows potent anti-tumor activity and dosing flexibility in vivo. Cancer Chemother Pharmacol. 2009 Aug 1.
Ref 543524(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. (Target id: 1936).

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