aurora kinase B

Target id: 1937

Nomenclature: aurora kinase B

Abbreviated Name: AurB

Family: Aurora kinase (Aur) family

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for aurora kinase B in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 344 17p13.1 AURKB aurora kinase B
Mouse - 345 11 B3 Aurkb aurora kinase B
Rat - 343 10 q24 Aurkb aurora kinase B
Previous and Unofficial Names
Aik2 | Aim1 | AIRK2 | ARK2 | serine/threonine-protein kinase 12 | serine/threonine-protein kinase 5 | STK-1 | STK12 | STK5
Database Links
BRENDA
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Human Aurora B Kinase in complex with INCENP and VX-680 (tozasertib)
PDB Id:  4AF3
Ligand:  tozasertib
Resolution:  2.75Å
Species:  Human
References:  9
Enzyme Reaction
EC Number: 2.7.11.1

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
barasertib-hQPA Hs Inhibition 8.3 pKd 7
pKd 8.3 (Kd 4.6x10-9 M) [7]
GSK1070916 Hs Inhibition 9.4 pKi 1
pKi 9.4 (Ki 3.8x10-10 M) [1]
tozasertib Hs Inhibition 7.7 pKi 14
pKi 7.7 (Ki 1.8x10-8 M) [14]
barasertib Hs Inhibition 9.4 pIC50 27
pIC50 9.4 (IC50 3.7x10-10 M) [27]
barasertib-hQPA Hs Inhibition >9.0 pIC50 22
pIC50 >9.0 (IC50 <1x10-9 M) This data refers to Compound 7 in Table 7 of the listed reference. [22]
compound 1 [PMID: 21742770] Hs Inhibition 8.6 pIC50 25
pIC50 8.6 (IC50 2.8x10-9 M) [25]
AT-9283 Hs Inhibition ~8.5 pIC50 16
pIC50 ~8.5 (IC50 ~3x10-9 M) [16]
AMG-900 Hs Inhibition 8.4 pIC50 21
pIC50 8.4 (IC50 4x10-9 M) [21]
compound 46 [PMID: 16451062] Hs Inhibition >8.1 pIC50 17
pIC50 >8.1 (IC50 <7x10-9 M) [17]
MLN-8054 Hs Inhibition 8.0 pIC50 2
pIC50 8.0 (IC50 9.3x10-9 M) [2]
TP-0903 Hs Inhibition 7.9 pIC50 19
pIC50 7.9 (IC50 1.24x10-8 M) [19]
compound 25 [PMID: 20855207] Hs Inhibition >7.9 pIC50 5
pIC50 >7.9 (IC50 <1.3x10-8 M) [5]
MK-5108 Hs Inhibition 7.8 pIC50 23
pIC50 7.8 (IC50 1.41x10-8 M) [23]
SU6656 Hs Inhibition 7.7 pIC50 4
pIC50 7.7 (IC50 1.9x10-8 M) [4]
SNS-314 Hs Inhibition 7.5 pIC50 20
pIC50 7.5 (IC50 3.1x10-8 M) [20]
compound 38 [PMID: 20817473] Hs Inhibition 7.3 pIC50 6
pIC50 7.3 (IC50 4.5x10-8 M) [6]
KW-2449 Hs Inhibition 7.3 pIC50 24
pIC50 7.3 (IC50 4.8x10-8 M) [24]
danusertib Hs Inhibition 7.1 pIC50 10
pIC50 7.1 (IC50 7.9x10-8 M) [10]
ZM447439 Hs Inhibition 7.0 pIC50 8
pIC50 7.0 (IC50 1x10-7 M) [8]
hesperadin Hs Inhibition 6.6 pIC50 15
pIC50 6.6 (IC50 2.5x10-7 M) [15]
aurora kinase inhibitor II Hs Inhibition 5.9 pIC50 11
pIC50 5.9 (IC50 1.25x10-6 M) [11]
GSK2334470 Hs Inhibition 5.5 pIC50 18
pIC50 5.5 (IC50 3.16x10-6 M) [18]
compound 10 [PMID: 19402633] Hs Inhibition 5.5 pIC50 2
pIC50 5.5 (IC50 3.4x10-6 M) [2]
DiscoveRx KINOMEscan® screen
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 7,26

Key to terms and symbols Click column headers to sort
Target used in screen: AURKB
Ligand Sp. Type Action Affinity Units
barasertib-hQPA Hs Inhibitor Inhibition 8.3 pKd
tozasertib Hs Inhibitor Inhibition 8.1 pKd
axitinib Hs Inhibitor Inhibition 8.0 pKd
lestaurtinib Hs Inhibitor Inhibition 7.8 pKd
staurosporine Hs Inhibitor Inhibition 7.7 pKd
foretinib Hs Inhibitor Inhibition 7.4 pKd
MLN-8054 Hs Inhibitor Inhibition 7.4 pKd
midostaurin Hs Inhibitor Inhibition 7.2 pKd
crizotinib Hs Inhibitor Inhibition 7.1 pKd
KW-2449 Hs Inhibitor Inhibition 7.1 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.

A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx


Reference: 3,13

Key to terms and symbols Click column headers to sort
Target used in screen: Aurora-B/Aurora B
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
midostaurin Hs Inhibitor Inhibition 3.0 1.0 3.0
K-252a Hs Inhibitor Inhibition 3.5 0.0 0.0
PDGF RTK inhibitor Hs Inhibitor Inhibition 4.3 2.0 -1.0
staurosporine Hs Inhibitor Inhibition 4.3 0.5 -0.5
tozasertib Hs Inhibitor Inhibition 4.9
JAK3 inhibitor VI Hs Inhibitor Inhibition 8.5 4.0 4.0
PKR inhibitor, negative control Hs Inhibitor Inhibition 9.2 51.0 2.0
SB 218078 Hs Inhibitor Inhibition 9.5 2.0 4.0
semaxanib Hs Inhibitor Inhibition 9.6 6.0 0.0
Syk inhibitor Hs Inhibitor Inhibition 10.5 3.0 0.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Tissue Distribution
Aurora kinase B (as part of the passenger complex) localise to centromeres from prometaphase to metaphase. Following chromatid separation, Aurora kinase B redistributes to midzone and persists at the midbody until cytokinesis is completed.
Species:  Human
Technique:  Transfected HeLa cells.
References:  12
Physiological Functions
Aurora kinase B is a component of the chromosomal passenger complex which functions to ensure accurate chromosome segregation and cell body division during mitosis.
Species:  Human
Tissue:  Transfected HeLA cells
References:  12

References

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1. Adams ND, Adams JL, Burgess JL, Chaudhari AM, Copeland RA, Donatelli CA, Drewry DH, Fisher KE, Hamajima T, Hardwicke MA et al.. (2010) Discovery of GSK1070916, a potent and selective inhibitor of Aurora B/C kinase. J. Med. Chem.53 (10): 3973-4001. [PMID:20420387]

2. Aliagas-Martin I, Burdick D, Corson L, Dotson J, Drummond J, Fields C, Huang OW, Hunsaker T, Kleinheinz T, Krueger E et al.. (2009) A class of 2,4-bisanilinopyrimidine Aurora A inhibitors with unusually high selectivity against Aurora B. J. Med. Chem.52 (10): 3300-7. [PMID:19402633]

3. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat. Biotechnol.29 (11): 1039-45. [PMID:22037377]

4. Bain J, Plater L, Elliott M, Shpiro N, Hastie CJ, McLauchlan H, Klevernic I, Arthur JS, Alessi DR, Cohen P. (2007) The selectivity of protein kinase inhibitors: a further update. Biochem. J.408 (3): 297-315. [PMID:17850214]

5. Belanger DB, Williams MJ, Curran PJ, Mandal AK, Meng Z, Rainka MP, Yu T, Shih NY, Siddiqui MA, Liu M et al.. (2010) Discovery of orally bioavailable imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors. Bioorg. Med. Chem. Lett.20 (22): 6739-43. [PMID:20855207]

6. Bindi S, Fancelli D, Alli C, Berta D, Bertrand JA, Cameron AD, Cappella P, Carpinelli P, Cervi G, Croci V et al.. (2010) Thieno[3,2-c]pyrazoles: a novel class of Aurora inhibitors with favorable antitumor activity. Bioorg. Med. Chem.18 (19): 7113-20. [PMID:20817473]

7. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat. Biotechnol.29 (11): 1046-51. [PMID:22037378]

8. Ditchfield C, Johnson VL, Tighe A, Ellston R, Haworth C, Johnson T, Mortlock A, Keen N, Taylor SS. (2003) Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores. J. Cell Biol.161 (2): 267-80. [PMID:12719470]

9. Elkins JM, Santaguida S, Musacchio A, Knapp S. (2012) Crystal structure of human aurora B in complex with INCENP and VX-680. J. Med. Chem.55 (17): 7841-8. [PMID:22920039]

10. Fancelli D, Moll J, Varasi M, Bravo R, Artico R, Berta D, Bindi S, Cameron A, Candiani I, Cappella P et al.. (2006) 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles: identification of a potent Aurora kinase inhibitor with a favorable antitumor kinase inhibition profile. J. Med. Chem.49 (24): 7247-51. [PMID:17125279]

11. Fedorov O, Marsden B, Pogacic V, Rellos P, Müller S, Bullock AN, Schwaller J, Sundström M, Knapp S. (2007) A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc. Natl. Acad. Sci. U.S.A.104 (51): 20523-8. [PMID:18077363]

12. Fu J, Bian M, Jiang Q, Zhang C. (2007) Roles of Aurora kinases in mitosis and tumorigenesis. Mol. Cancer Res.5 (1): 1-10. [PMID:17259342]

13. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem. J.451 (2): 313-28. [PMID:23398362]

14. Harrington EA, Bebbington D, Moore J, Rasmussen RK, Ajose-Adeogun AO, Nakayama T, Graham JA, Demur C, Hercend T, Diu-Hercend A et al.. (2004) VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Nat. Med.10 (3): 262-7. [PMID:14981513]

15. Hauf S, Cole RW, LaTerra S, Zimmer C, Schnapp G, Walter R, Heckel A, van Meel J, Rieder CL, Peters JM. (2003) The small molecule Hesperadin reveals a role for Aurora B in correcting kinetochore-microtubule attachment and in maintaining the spindle assembly checkpoint. J. Cell Biol.161 (2): 281-94. [PMID:12707311]

16. Howard S, Berdini V, Boulstridge JA, Carr MG, Cross DM, Curry J, Devine LA, Early TR, Fazal L, Gill AL et al.. (2009) Fragment-based discovery of the pyrazol-4-yl urea (AT9283), a multitargeted kinase inhibitor with potent aurora kinase activity. J. Med. Chem.52 (2): 379-88. [PMID:19143567]

17. Jung FH, Pasquet G, Lambert-van der Brempt C, Lohmann JJ, Warin N, Renaud F, Germain H, De Savi C, Roberts N, Johnson T et al.. (2006) Discovery of novel and potent thiazoloquinazolines as selective Aurora A and B kinase inhibitors. J. Med. Chem.49 (3): 955-70. [PMID:16451062]

18. Medina JR, Becker CJ, Blackledge CW, Duquenne C, Feng Y, Grant SW, Heerding D, Li WH, Miller WH, Romeril SP et al.. (2011) Structure-based design of potent and selective 3-phosphoinositide-dependent kinase-1 (PDK1) inhibitors. J. Med. Chem.54 (6): 1871-95. [PMID:21341675]

19. Mollard A, Warner SL, Call LT, Wade ML, Bearss JJ, Verma A, Sharma S, Vankayalapati H, Bearss DJ. (2011) Design, Synthesis and Biological Evaluation of a Series of Novel Axl Kinase Inhibitors. ACS Med Chem Lett2 (12): 907-912. [PMID:22247788]

20. Oslob JD, Romanowski MJ, Allen DA, Baskaran S, Bui M, Elling RA, Flanagan WM, Fung AD, Hanan EJ, Harris S et al.. (2008) Discovery of a potent and selective aurora kinase inhibitor. Bioorg. Med. Chem. Lett.18 (17): 4880-4. [PMID:18678489]

21. Payton M, Bush TL, Chung G, Ziegler B, Eden P, McElroy P, Ross S, Cee VJ, Deak HL, Hodous BL et al.. (2010) 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.70 (23): 9846-54. [PMID:20935223]

22. Pollard JR, Mortimore M. (2009) Discovery and development of aurora kinase inhibitors as anticancer agents. J. Med. Chem.52 (9): 2629-51. [PMID:19320489]

23. Shimomura T, Hasako S, Nakatsuru Y, Mita T, Ichikawa K, Kodera T, Sakai T, Nambu T, Miyamoto M, Takahashi I et al.. (2010) MK-5108, a highly selective Aurora-A kinase inhibitor, shows antitumor activity alone and in combination with docetaxel. Mol. Cancer Ther.9 (1): 157-66. [PMID:20053775]

24. Shiotsu Y, Kiyoi H, Ishikawa Y, Tanizaki R, Shimizu M, Umehara H, Ishii K, Mori Y, Ozeki K, Minami Y et al.. (2009) KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation. Blood114 (8): 1607-17. [PMID:19541823]

25. Weïwer M, Spoonamore J, Wei J, Guichard B, Ross NT, Masson K, Silkworth W, Dandapani S, Palmer M, Scherer CA et al.. (2012) A Potent and Selective Quinoxalinone-Based STK33 Inhibitor Does Not Show Synthetic Lethality in KRAS-Dependent Cells. ACS Med Chem Lett3 (12): 1034-1038. [PMID:23256033]

26. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem. Biol.17 (11): 1241-9. [PMID:21095574]

27. Yang J, Ikezoe T, Nishioka C, Tasaka T, Taniguchi A, Kuwayama Y, Komatsu N, Bandobashi K, Togitani K, Koeffler HP et al.. (2007) AZD1152, a novel and selective aurora B kinase inhibitor, induces growth arrest, apoptosis, and sensitization for tubulin depolymerizing agent or topoisomerase II inhibitor in human acute leukemia cells in vitro and in vivo. Blood110 (6): 2034-40. [PMID:17495131]

How to cite this page

Aurora kinase (Aur) family: aurora kinase B. Last modified on 22/11/2016. Accessed on 17/10/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1937.