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 | |||||
| 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 | [1], [2] |
| ABT-348 | Drug Info | Phase 2 | Hematological malignancies | [3] | |
| PHA-739358 | Drug Info | Phase 2 | Prostate cancer | [4], [5] | |
| AMG 900 | Drug Info | Phase 1 | Solid tumours | [6], [7] | |
| GSK1070916 | Drug Info | Phase 1 | Advanced solid tumor | [8], [9] | |
| GSK1070916A | Drug Info | Phase 1 | Solid tumours | [10] | |
| HPP-607 | Drug Info | Phase 1 | Cancer | [11] | |
| SNS-314 | Drug Info | Phase 1 | Solid tumours | [12] | |
| MK-6592 | Drug Info | Discontinued in Phase 1 | Cancer | [13] | |
| Inhibitor | 2np8 | Drug Info | [14] | ||
| 6-bromoindirubin-3-oxime | Drug Info | [15] | |||
| 7-bromoindirubin-3-acetoxime | Drug Info | [15] | |||
| 7-bromoindirubin-3-oxime | Drug Info | [15] | |||
| 7-chloroindirubin-3-oxime | Drug Info | [15] | |||
| 7-fluoroindirubin-3-acetoxime | Drug Info | [15] | |||
| 7-fluoroindirubin-3-oxime | Drug Info | [15] | |||
| 7-iodoindirubin-3-oxime | Drug Info | [15] | |||
| BMS-739562 | Drug Info | [16] | |||
| BPR1K-0224 | Drug Info | [16] | |||
| compound 10 | Drug Info | [17] | |||
| compound 16 | Drug Info | [18] | |||
| compound 25 | Drug Info | [19] | |||
| compound 46 | Drug Info | [20] | |||
| Glycyl-H 1152 | Drug Info | [21] | |||
| HPP-607 | Drug Info | [16] | |||
| Indirubin-3-acetoxime | Drug Info | [15] | |||
| Indirubin-3-methoxime | Drug Info | [15] | |||
| Indirubin-3-oxime | Drug Info | [15] | |||
| K00244 | Drug Info | [22] | |||
| MK-6592 | Drug Info | [23] | |||
| MP-529 | Drug Info | [16] | |||
| PHA-739358 | Drug Info | [24] | |||
| quinazoline deriv. 1 | Drug Info | [25] | |||
| SNS-314 | Drug Info | [26], [27], [28], [29] | |||
| SNS-314 prodrugs | Drug Info | [16] | |||
| SU 6656 | Drug Info | [30] | |||
| Modulator | ABT-348 | Drug Info | [31] | ||
| AMG 900 | Drug Info | [6] | |||
| GSK1070916 | Drug Info | [32] | |||
| GSK1070916A | Drug Info | [33], [32] | |||
| 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 1 | ClinicalTrials.gov (NCT01511289) Radotinib Versus Imatinib in Newly Diagnosed Philadelphia Chromosome and Chronic Myeloid Leukemia Chronic Phase Patients. U.S. National Institutes of Health. | ||||
| REF 2 | (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 3 | ClinicalTrials.gov (NCT02478320) Phase II Study of Ilorasertib (ABT348) in Patients With CDKN2A Deficient Solid Tumors. | ||||
| REF 4 | (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 5 | 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 6 | 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 7 | (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 8 | (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 9 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032133) | ||||
| REF 10 | ClinicalTrials.gov (NCT01118611) Aurora B/C Kinase Inhibitor GSK1070916A in Treating Patients With Advanced Solid Tumors. U.S. National Institutes of Health. | ||||
| REF 11 | ClinicalTrials.gov (NCT00939172) TTP607 in Refractory Solid Malignancies. U.S. National Institutes of Health. | ||||
| REF 12 | ClinicalTrials.gov (NCT00519662) Safety and Tolerability Study of SNS-314 for Advanced Solid Tumors. U.S. National Institutes of Health. | ||||
| REF 13 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024789) | ||||
| REF 14 | Structural 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 15 | 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 16 | (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). | ||||
| REF 17 | A 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 18 | Pyrrolo-pyrimidones: a novel class of MK2 inhibitors with potent cellular activity. Bioorg Med Chem Lett. 2008 Dec 1;18(23):6142-6. | ||||
| REF 19 | Discovery of orally bioavailable imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors. Bioorg Med Chem Lett. 2010 Nov 15;20(22):6739-43. | ||||
| REF 20 | J Med Chem. 2006 Feb 9;49(3):955-70.Discovery of novel and potent thiazoloquinazolines as selective Aurora A and B kinase inhibitors. | ||||
| REF 21 | Development 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 22 | The discovery of the potent aurora inhibitor MK-0457 (VX-680). Bioorg Med Chem Lett. 2009 Jul 1;19(13):3586-92. | ||||
| REF 23 | Clinical experience with aurora kinase inhibitors: a review. Oncologist. 2009 Aug;14(8):780-93. | ||||
| REF 24 | 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. | ||||
| REF 25 | Proc 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 26 | Water-soluble prodrugs of an Aurora kinase inhibitor. Bioorg Med Chem Lett. 2009 Mar 1;19(5):1409-12. Epub 2009 Jan 19. | ||||
| REF 27 | Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2009 Jan-Feb;31(1):47-57. | ||||
| REF 28 | 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 29 | SNS-314, a pan-Aurora kinase inhibitor, shows potent anti-tumor activity and dosing flexibility in vivo. Cancer Chemother Pharmacol. 2009 Aug 1. | ||||
| REF 30 | Biochem J. 2007 Dec 15;408(3):297-315.The selectivity of protein kinase inhibitors: a further update. | ||||
| REF 31 | Preclinical 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 32 | J Med Chem. 2010 May 27;53(10):3973-4001.Discovery of GSK1070916, a potent and selective inhibitor of Aurora B/C kinase. | ||||
| REF 33 | GSK1070916, 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. | ||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.