Target Information
| Target General Information | Top | |||||
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| Target ID |
T77764
(Former ID: TTDR01420)
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| Target Name |
Aurora B messenger RNA (AURKB mRNA)
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| Synonyms |
Serine/threonine-protein kinase aurora-B (mRNA); Serine/threonine-protein kinase 5 (mRNA); Serine/threonine-protein kinase 12 (mRNA); Serine/threonine protein kinase 12 (mRNA); STK5 (mRNA); STK12 (mRNA); Aurora/IPL1-related kinase 2 (mRNA); Aurora-related kinase 2 (mRNA); Aurora-B (mRNA); Aurora-2 kinase (mRNA); Aurora-2 (mRNA); Aurora- and Ipl1-like midbody-associated protein 1 (mRNA); Aurora 1 (mRNA); ARK2 (mRNA); ARK-2 (mRNA); AIRK2 (mRNA); AIM1 (mRNA); AIM-1 (mRNA); AIK2 (mRNA)
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| Gene Name |
AURKB
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Prostate cancer [ICD-11: 2C82] | |||||
| Function |
The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Involved in the bipolar attachment of spindle microtubules to kinetochores and is a key regulator for the onset of cytokinesis during mitosis. Required for central/midzone spindle assembly and cleavage furrow formation. Key component of the cytokinesis checkpoint, a process required to delay abscission to prevent both premature resolution of intercellular chromosome bridges and accumulation of DNA damage: phosphorylates CHMP4C, leading to retain abscission-competent VPS4 (VPS4A and/or VPS4B) at the midbody ring until abscission checkpoint signaling is terminated at late cytokinesis. AURKB phosphorylates the CPC complex subunits BIRC5/survivin, CDCA8/borealin and INCENP. Phosphorylation of INCENP leads to increased AURKB activity. Other known AURKB substrates involved in centromeric functions and mitosis are CENPA, DES/desmin, GPAF, KIF2C, NSUN2, RACGAP1, SEPT1, VIM/vimentin, HASPIN, and histone H3. A positive feedback loop involving HASPIN and AURKB contributes to localization of CPC to centromeres. Phosphorylation of VIM controls vimentin filament segregation in cytokinetic process, whereas histone H3 is phosphorylated at 'Ser-10' and 'Ser-28' during mitosis (H3S10ph and H3S28ph, respectively). A positive feedback between HASPIN and AURKB contributes to CPC localization. AURKB is also required for kinetochore localization of BUB1 and SGO1. Phosphorylation of p53/TP53 negatively regulates its transcriptional activity. Key regulator of active promoters in resting B- and T-lymphocytes: acts by mediating phosphorylation of H3S28ph at active promoters in resting B-cells, inhibiting RNF2/RING1B-mediated ubiquitination of histone H2A and enhancing binding and activity of the USP16 deubiquitinase at transcribed genes. Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis.
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| BioChemical Class |
mRNA target
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| UniProt ID | ||||||
| EC Number |
EC 2.7.11.1
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| Sequence |
MAQKENSYPWPYGRQTAPSGLSTLPQRVLRKEPVTPSALVLMSRSNVQPTAAPGQKVMEN
SSGTPDILTRHFTIDDFEIGRPLGKGKFGNVYLAREKKSHFIVALKVLFKSQIEKEGVEH QLRREIEIQAHLHHPNILRLYNYFYDRRRIYLILEYAPRGELYKELQKSCTFDEQRTATI MEELADALMYCHGKKVIHRDIKPENLLLGLKGELKIADFGWSVHAPSLRRKTMCGTLDYL PPEMIEGRMHNEKVDLWCIGVLCYELLVGNPPFESASHNETYRRIVKVDLKFPASVPMGA QDLISKLLRHNPSERLPLAQVSAHPWVRANSRRVLPPSALQSVA Click to Show/Hide
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| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | PHA-739358 | Drug Info | Phase 2 | Prostate cancer | [2], [3] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 18 Inhibitor drugs | + | ||||
| 1 | PHA-739358 | Drug Info | [1] | |||
| 2 | 4-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine | Drug Info | [4] | |||
| 3 | 6-bromoindirubin-3-oxime | Drug Info | [5] | |||
| 4 | 7-bromoindirubin-3-oxime | Drug Info | [5] | |||
| 5 | 7-chloroindirubin-3-oxime | Drug Info | [5] | |||
| 6 | 7-fluoroindirubin-3-acetoxime | Drug Info | [5] | |||
| 7 | 7-fluoroindirubin-3-oxime | Drug Info | [5] | |||
| 8 | 7-iodoindirubin-3-oxime | Drug Info | [5] | |||
| 9 | CGP-57380 | Drug Info | [6] | |||
| 10 | HESPERADIN | Drug Info | [7] | |||
| 11 | Indirubin-3'-monoxime | Drug Info | [5] | |||
| 12 | Indirubin-3-acetoxime | Drug Info | [5] | |||
| 13 | Indirubin-3-methoxime | Drug Info | [5] | |||
| 14 | PMID16451062C46 | Drug Info | [7] | |||
| 15 | PMID20855207C25 | Drug Info | [9] | |||
| 16 | PMID21742770C1 | Drug Info | [10] | |||
| 17 | quinazoline deriv. 1 | Drug Info | [11] | |||
| 18 | SU 6656 | Drug Info | [6] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| PID Pathway | [+] 5 PID Pathways | + | ||||
| 1 | Aurora B signaling | |||||
| 2 | Signaling by Aurora kinases | |||||
| 3 | Aurora C signaling | |||||
| 4 | FOXM1 transcription factor network | |||||
| 5 | Aurora A signaling | |||||
| Reactome | [+] 5 Reactome Pathways | + | ||||
| 1 | APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 | |||||
| 2 | Separation of Sister Chromatids | |||||
| 3 | Resolution of Sister Chromatid Cohesion | |||||
| 4 | RHO GTPases Activate Formins | |||||
| 5 | Mitotic Prometaphase | |||||
| WikiPathways | [+] 6 WikiPathways | + | ||||
| 1 | Mitotic Metaphase and Anaphase | |||||
| 2 | Mitotic Prometaphase | |||||
| 3 | Regulation of Microtubule Cytoskeleton | |||||
| 4 | miR-targeted genes in lymphocytes - TarBase | |||||
| 5 | miR-targeted genes in epithelium - TarBase | |||||
| 6 | APC/C-mediated degradation of cell cycle proteins | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Potent and selective Aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition. J Med Chem. 2005 Apr 21;48(8):3080-4. | |||||
| REF 2 | URL: 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 3 | 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 4 | Discovery of a new series of Aurora inhibitors through truncation of GSK1070916. Bioorg Med Chem Lett. 2010 Apr 15;20(8):2552-5. | |||||
| REF 5 | An integrated computational approach to the phenomenon of potent and selective inhibition of aurora kinases B and C by a series of 7-substituted in... J Med Chem. 2007 Aug 23;50(17):4027-37. | |||||
| REF 6 | The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315. | |||||
| REF 7 | Discovery of novel and potent thiazoloquinazolines as selective Aurora A and B kinase inhibitors. J Med Chem. 2006 Feb 9;49(3):955-70. | |||||
| REF 8 | US patent application no. 7,375,212, Modulation of Aurora B expression. | |||||
| REF 9 | 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 10 | A Potent and Selective Quinoxalinone-Based STK33 Inhibitor Does Not Show Synthetic Lethality in KRAS-Dependent Cells. ACS Med Chem Lett. 2012 Dec 13;3(12):1034-1038. | |||||
| REF 11 | A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8. | |||||
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