aurora kinase A | Aurora kinase (Aur) family | IUPHAR/BPS Guide to PHARMACOLOGY

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aurora kinase A

Target not currently curated in GtoImmuPdb

Target id: 1936

Nomenclature: aurora kinase A

Abbreviated Name: AurA

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

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 403 20q13 AURKA aurora kinase A
Mouse - 417 2 H3 Aurka aurora kinase A
Rat - 397 3 q42 Aurka aurora kinase A
Previous and Unofficial Names
ARK1 | AurA | Aurora 2 | Aurora family kinase 1 | ratAurA | serine/threonine kinase 15 | serine/threonine kinase 6 | STK15 | STK6
Database Links
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
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:  Structure of AuroraA with pyridyl-pyrimidine urea inhibitor
PDB Id:  3EFW
Resolution:  2.29Å
Species:  Human
References:  9
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of Aurora-A Protein Kinase
PDB Id:  1MQ4
Resolution:  1.9Å
Species:  Human
References:  26
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 Parameter Reference
tozasertib Hs Inhibition 8.4 pKd 10
pKd 8.4 (Kd 3.9x10-9 M) [10]
MLN-8054 Hs Inhibition 8.2 pKd 10
pKd 8.2 (Kd 6.5x10-9 M) [10]
RG-1530 Hs Inhibition 7.0 pKd 36
pKd 7.0 (Kd 9.6x10-8 M) [36]
tozasertib Hs Inhibition 9.2 pKi 17
pKi 9.2 (Ki 6x10-10 M) [17]
GSK-3 inhibitor XIII Hs Inhibition 7.2 pKi 6
pKi 7.2 (Ki 5.8x10-8 M) [6]
GSK1070916 Hs Inhibition 6.3 pKi 1
pKi 6.3 (Ki 4.9x10-7 M) [1]
VTX-11e Hs Inhibition 6.3 pKi 4
pKi 6.3 (Ki 5.4x10-7 M) [4]
MK-5108 Hs Inhibition 10.2 pIC50 32
pIC50 10.2 (IC50 6.4x10-11 M) [32]
alisertib Hs Inhibition 9.0 pIC50 29
pIC50 9.0 (IC50 1x10-9 M) [29]
compound 46 [PMID: 16451062] Hs Inhibition >9.0 pIC50 20
pIC50 >9.0 (IC50 <1x10-9 M) [20]
MLN-8054 Hs Inhibition 8.4 – 9.0 pIC50 2,23
pIC50 8.4 – 9.0 (IC50 4x10-9 – 1x10-9 M) [2,23]
AT-9283 Hs Inhibition ~8.5 pIC50 18
pIC50 ~8.5 (IC50 ~3x10-9 M) [18]
TP-0903 Hs Inhibition 8.5 pIC50 25
pIC50 8.5 (IC50 3x10-9 M) [25]
compound 10 [PMID: 19402633] Hs Inhibition 8.5 pIC50 2
pIC50 8.5 (IC50 3.4x10-9 M) [2]
compound 25 [PMID: 20855207] Hs Inhibition >8.4 pIC50 7
pIC50 >8.4 (IC50 <4x10-9 M) [7]
GSK143 Hs Inhibition 8.3 pIC50 21
pIC50 8.3 (IC50 4.8x10-9 M) [21]
Description: Enzyme inhibition assay using recombinant human protein
AMG-900 Hs Inhibition 8.3 pIC50 28
pIC50 8.3 (IC50 5x10-9 M) [28]
SNS-314 Hs Inhibition 8.1 pIC50 27
pIC50 8.1 (IC50 9x10-9 M) [27]
danusertib Hs Inhibition 7.9 pIC50 12
pIC50 7.9 (IC50 1.3x10-8 M) [12]
ENMD-2076 Hs Inhibition 7.8 pIC50 29
pIC50 7.8 (IC50 1.4x10-8 M) [29]
JNJ-7706621 Hs Inhibition 7.7 pIC50 19
pIC50 7.7 (IC50 1.8x10-8 M) [19]
compound 38 [PMID: 20817473] Hs Inhibition 7.7 pIC50 8
pIC50 7.7 (IC50 1.8x10-8 M) [8]
aurora kinase inhibitor III Hs Inhibition 7.4 pIC50 35
pIC50 7.4 (IC50 4.2x10-8 M) [35]
KW-2449 Hs Inhibition 7.3 pIC50 33
pIC50 7.3 (IC50 4.8x10-8 M) [33]
Cdk2 inhibitor IV Hs Inhibition 7.2 pIC50 19
pIC50 7.2 (IC50 6.7x10-8 M) [19]
compound 16 [PMID: 18945615] Hs Inhibition 7.0 pIC50 31
pIC50 7.0 (IC50 9.3x10-8 M) [31]
ZM447439 Hs Inhibition 7.0 pIC50 11
pIC50 7.0 (IC50 1x10-7 M) [11]
ilorasertib Hs Inhibition 6.9 pIC50 16
pIC50 6.9 (IC50 1.2x10-7 M) [16]
Description: Measuring inhibition of kinase activity in a biochemical assay.
PF-562271 Hs Inhibition 6.8 pIC50 30
pIC50 6.8 (IC50 1.45x10-7 M) [30]
aurora kinase inhibitor II Hs Inhibition 6.5 pIC50 13
pIC50 6.5 (IC50 3.1x10-7 M) [13]
barasertib Hs Inhibition 5.9 pIC50 38
pIC50 5.9 (IC50 1.368x10-6 M) [38]
Rho kinase inhibitor IV Hs Inhibition 5.6 pIC50 34
pIC50 5.6 (IC50 2.35x10-6 M) [34]
GSK2334470 Hs Inhibition <5.0 pIC50 24
pIC50 <5.0 (IC50 >1x10-5 M) [24]
GSK2646264 Hs Inhibition <4.3 pIC50 5
pIC50 <4.3 (IC50 >5.012x10-5 M) [5]
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: 10,37

Key to terms and symbols Click column headers to sort
Target used in screen: AURKA
Ligand Sp. Type Action Affinity Parameter
tozasertib Hs Inhibitor Inhibition 8.4 pKd
MLN-8054 Hs Inhibitor Inhibition 8.2 pKd
lestaurtinib Hs Inhibitor Inhibition 7.8 pKd
staurosporine Hs Inhibitor Inhibition 7.8 pKd
NVP-TAE684 Hs Inhibitor Inhibition 7.4 pKd
axitinib Hs Inhibitor Inhibition 7.1 pKd
midostaurin Hs Inhibitor Inhibition 6.9 pKd
tamatinib Hs Inhibitor Inhibition 6.8 pKd
crizotinib Hs Inhibitor Inhibition 6.6 pKd
barasertib-hQPA Hs Inhibitor Inhibition 6.4 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: 3,15

Key to terms and symbols Click column headers to sort
Target used in screen: Aurora-A/Aurora A
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 1.4 1.0 10.0
staurosporine Hs Inhibitor Inhibition 2.4 -5.5 -2.0
Cdk2 inhibitor IV Hs Inhibitor Inhibition 3.0 1.0 5.0
midostaurin Hs Inhibitor Inhibition 4.5 -3.0 -2.0
K-252a Hs Inhibitor Inhibition 4.6 2.0 -1.0
tozasertib Hs Inhibitor Inhibition 5.2
indirubin derivative E804 Hs Inhibitor Inhibition 9.8 7.0 3.0
JNJ-7706621 Hs Inhibitor Inhibition 13.0 0.0 -2.0
SU6656 Hs Inhibitor Inhibition 16.1 36.0 13.0
GSK-3 inhibitor IX Hs Inhibitor Inhibition 17.1 31.0 25.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Tissue Distribution
Aurora kinase A localises to the centrosomes during DNA duplication in the S phase and migrates to spindle poles during mitosis.
Species:  Human
Technique:  Transfected HeLa cells.
References:  14
Physiological Functions
Aurora kinase A plays a central role in centrosome regulation and mitotic spindle formation.
Species:  Human
Tissue:  Transfected HeLa cells.
References:  14
Physiological Consequences of Altering Gene Expression
Aurora kinase A knock-out mice are not viable. Aurka−/− embryos die before the 16-cell stage.
Species:  Mouse
Tissue: 
Technique:  Gene knock-out.
References:  22
Clinically-Relevant Mutations and Pathophysiology
Disease:  Colorectal cancer
Disease Ontology: DOID:9256
OMIM: 114500

References

Show »

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. Aronov AM, Tang Q, Martinez-Botella G, Bemis GW, Cao J, Chen G, Ewing NP, Ford PJ, Germann UA, Green J et al.. (2009) Structure-guided design of potent and selective pyrimidylpyrrole inhibitors of extracellular signal-regulated kinase (ERK) using conformational control. J. Med. Chem., 52 (20): 6362-8. [PMID:19827834]

5. Barker MD, Liddle J, Atkinson FL, Wilson DM, Dickson MC, Ramirez-Molina C, Lewis H, Davis RP, Somers DO, Neu M et al.. (2018) Discovery of potent and selective Spleen Tyrosine Kinase inhibitors for the topical treatment of inflammatory skin disease. Bioorg. Med. Chem. Lett., 28 (21): 3458-3462. [PMID:30249354]

6. Bebbington D, Binch H, Charrier JD, Everitt S, Fraysse D, Golec J, Kay D, Knegtel R, Mak C, Mazzei F et al.. (2009) The discovery of the potent aurora inhibitor MK-0457 (VX-680). Bioorg. Med. Chem. Lett., 19 (13): 3586-92. [PMID:19447622]

7. 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]

8. 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]

9. Cee VJ, Cheng AC, Romero K, Bellon S, Mohr C, Whittington DA, Bak A, Bready J, Caenepeel S, Coxon A et al.. (2009) Pyridyl-pyrimidine benzimidazole derivatives as potent, selective, and orally bioavailable inhibitors of Tie-2 kinase. Bioorg. Med. Chem. Lett., 19 (2): 424-7. [PMID:19062275]

10. 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]

11. 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]

12. 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]

13. 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]

14. 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]

15. 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]

16. Glaser KB, Li J, Marcotte PA, Magoc TJ, Guo J, Reuter DR, Tapang P, Wei RQ, Pease LJ, Bui MH et al.. (2012) 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., 343 (3): 617-27. [PMID:22935731]

17. 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]

18. 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]

19. Jorda R, Hendrychová D, Voller J, Řezníčková E, Gucký T, Kryštof V. (2018) How Selective Are Pharmacological Inhibitors of Cell-Cycle-Regulating Cyclin-Dependent Kinases?. J. Med. Chem., 61 (20): 9105-9120. [PMID:30234987]

20. 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]

21. Liddle J, Atkinson FL, Barker MD, Carter PS, Curtis NR, Davis RP, Douault C, Dickson MC, Elwes D, Garton NS et al.. (2011) Discovery of GSK143, a highly potent, selective and orally efficacious spleen tyrosine kinase inhibitor. Bioorg. Med. Chem. Lett., 21 (20): 6188-94. [PMID:21903390]

22. Lu LY, Wood JL, Ye L, Minter-Dykhouse K, Saunders TL, Yu X, Chen J. (2008) Aurora A is essential for early embryonic development and tumor suppression. J. Biol. Chem., 283 (46): 31785-90. [PMID:18801727]

23. Manfredi MG, Ecsedy JA, Meetze KA, Balani SK, Burenkova O, Chen W, Galvin KM, Hoar KM, Huck JJ, LeRoy PJ et al.. (2007) Antitumor activity of MLN8054, an orally active small-molecule inhibitor of Aurora A kinase. Proc. Natl. Acad. Sci. U.S.A., 104 (10): 4106-11. [PMID:17360485]

24. 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]

25. 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 Lett, 2 (12): 907-912. [PMID:22247788]

26. Nowakowski J, Cronin CN, McRee DE, Knuth MW, Nelson CG, Pavletich NP, Rogers J, Sang BC, Scheibe DN, Swanson RV et al.. (2002) Structures of the cancer-related Aurora-A, FAK, and EphA2 protein kinases from nanovolume crystallography. Structure, 10 (12): 1659-67. [PMID:12467573]

27. 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]

28. 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]

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

30. Roberts WG, Ung E, Whalen P, Cooper B, Hulford C, Autry C, Richter D, Emerson E, Lin J, Kath J et al.. (2008) Antitumor activity and pharmacology of a selective focal adhesion kinase inhibitor, PF-562,271. Cancer Res., 68 (6): 1935-44. [PMID:18339875]

31. Schlapbach A, Feifel R, Hawtin S, Heng R, Koch G, Moebitz H, Revesz L, Scheufler C, Velcicky J, Waelchli R et al.. (2008) Pyrrolo-pyrimidones: a novel class of MK2 inhibitors with potent cellular activity. Bioorg. Med. Chem. Lett., 18 (23): 6142-6. [PMID:18945615]

32. 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]

33. 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. Blood, 114 (8): 1607-17. [PMID:19541823]

34. Tamura M, Nakao H, Yoshizaki H, Shiratsuchi M, Shigyo H, Yamada H, Ozawa T, Totsuka J, Hidaka H. (2005) Development of specific Rho-kinase inhibitors and their clinical application. Biochim. Biophys. Acta, 1754 (1-2): 245-52. [PMID:16213195]

35. Tari LW, Hoffman ID, Bensen DC, Hunter MJ, Nix J, Nelson KJ, McRee DE, Swanson RV. (2007) Structural basis for the inhibition of Aurora A kinase by a novel class of high affinity disubstituted pyrimidine inhibitors. Bioorg. Med. Chem. Lett., 17 (3): 688-91. [PMID:17157005]

36. Tovar C, Higgins B, Deo D, Kolinsky K, Liu JJ, Heimbrook DC, Vassilev LT. (2010) Small-molecule inducer of cancer cell polyploidy promotes apoptosis or senescence: Implications for therapy. Cell Cycle, 9 (16): 3364-75. [PMID:20814247]

37. 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]

38. 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. Blood, 110 (6): 2034-40. [PMID:17495131]

How to cite this page

Aurora kinase (Aur) family: aurora kinase A. Last modified on 12/04/2019. Accessed on 23/05/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1936.