Discovery of a new series of Aurora inhibitors through truncation of GSK1070916

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 8, 2010, Pages 2552-2555

  Medina, Jesus R ^a   Grant, Seth W ^a   Axten, Jeffrey M ^a   Miller, William H ^a   Donatelli, Carla A ^a   Hardwicke, Mary Ann ^a   Oleykowski, Catherine A ^a   Liao, Qiaoyin ^a   Plant, Ramona ^a   Xiang, Hong ^a  

^a GLAXOSMITHKLINE   (United States)

Author keywords

Aurora inhibitors; BEI; Cellular phenotype; FACS; FBDD; Lead generation

Indexed keywords

AURORA A KINASE; AURORA B KINASE; AURORA KINASE INHIBITOR; GSK 1070916; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; DRUG MECHANISM; DRUG POTENCY; ENZYME INHIBITION; FLUORESCENCE ACTIVATED CELL SORTING; HUMAN; HUMAN CELL; NONHUMAN; PHENOTYPE; STRUCTURE ACTIVITY RELATION;

AZA COMPOUNDS; CELL LINE, TUMOR; DRUG DISCOVERY; FLOW CYTOMETRY; HUMANS; INDOLES; PROTEIN KINASE INHIBITORS; PROTEIN-SERINE-THREONINE KINASES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 77950035129     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.02.091     Document Type: Article

References (23)

1. Keseru G.M., and Makara G.M. Nat. Rev. Drug Disc. 8 (2009) 203
2. Keseru G.M., and Makara G.M. Drug Discovery Today 11 (2006) 741
3. Murray C.W., and Rees D.C. Nat. Chem. 1 (2009) 187
4. Congreve M., Chessari G., Tisi D., and Woodhead A.J. J. Med. Chem. 51 (2008) 3661
5. Hajduk P.J., and Greer J. Nat. Rev. Drug Disc. 6 (2007) 211
6. Hajduk P.J. J. Med. Chem. 49 (2006) 6972
7. Bembenek S.D., Tounge B.A., and Reynolds C.H. Drug Discovery Today 14 (2009) 278
8. Abad-Zapatero C. Expert Opin. Drug Discovery 2 (2007) 469
9. Abad-Zapatero C., and Metz J.T. Drug Discovery Today 10 (2005) 464
10. Pollard J.R., and Mortimore M. J. Med. Chem. 52 (2009) 2629
11. Carmena M., and Earnshaw W.C. Nat. Rev. Mol. Cell Biol. 4 (2003) 842
12. Garuti L., Roberti M., and Bottegoni G. Curr. Med. Chem. 16 (2009) 1949
13. Cheung C.H.A., Coumar M.S., Hsieh H.-P., and Chang J.-Y. Expert Opin. Investig. Drugs 18 (2009) 379
14. Keen N., and Taylor S. Nat. Rev. Cancer 4 (2004) 927
15. Kallio M.J., McCleland M.L., Stukenberg P.T., and Gorbsky G.J. Curr. Biol. 12 (2002) 900
16. Ditchfield C., Johnson V., Tighe A., Ellston R., Haworth C., Johnson T., Mortlock A., Keen N., and Taylor S.S. J. Cell Biol. 161 (2003) 267
17. Hauf S., Cole R.W., LaTerra S., Zimmer C., Schnapp G., Walter R., Heckel A., van Meel J., Rieder C.L., and Peters J.-M. J. Cell Biol. 161 (2003) 281
18. Anderson K., Lai Z., McDonald O.B., Stuart J.D., Nartey E.N., Hardwicke M.A., Newlander K., Dhanak D., Adams J., Patrick D., Copeland R.A., Tummino P.J., and Yang J. Biochem. J. 420 (2009) 259
19. Hardwicke M.A., Oleykowski C.A., Plant R., Wang J., Liao Q., Moss K., Newlander K., Adams J.L., Dhanak D., Yang J., Lai Z., Sutton D., and Patrick D. Mol. Cancer Ther. 8 (2009) 1808
20. A description of the lead optimization efforts culminating in the identification of GSK1070916 was submitted for publication elsewhere.
21. Ralph J.M., Faitg T.H., Silva D.J., Feng Y., Blackledge C.W., and Adams J.L. Tetrahedron Lett. 50 (2009) 1377
22. 50 was within 50-fold the Aurora B activity.
23. Crisp G.T., Turner P.D., and Stephens K.A. J. Organomet. Chem. 570 (1998) 219