ARK1|AurA|Aurora 2|Aurora family kinase 1|ratAurA|serine/threonine kinase 15|serine/threonine kinase 6|STK15|STK6 Download all structure-activity data for this target as a CSV file 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 1 M and 10 M against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5 M 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 Aurora kinase A localises to the centrosomes during DNA duplication in the S phase and migrates to spindle poles during mitosis. Aurora kinase A plays a central role in centrosome regulation and mitotic spindle formation. Physiological Consequences of Altering Gene Expression Aurora kinase A knock-out mice are not viable. Aurka−/− embryos die before the 16-cell stage. Clinically-Relevant Mutations and Pathophysiology 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. 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. 3. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR.(2011)Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. 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. 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. 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). 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. 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. 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. 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. 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. 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. 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. 14. Fu J, Bian M, Jiang Q, Zhang C.(2007)Roles of Aurora kinases in mitosis and tumorigenesis. 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. 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. 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. 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. 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?. 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. 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. 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. 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. 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. 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. 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. 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. 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. 29. Pollard JR, Mortimore M.(2009)Discovery and development of aurora kinase inhibitors as anticancer agents. 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. 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. 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. 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. 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. 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. 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. 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. 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. Aurora kinase (Aur) family: aurora kinase A. Last modified on 12/04/2019. Accessed on 18/05/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1936.