Identification of isothiazole-4-carboxamidines derivatives as a novel class of allosteric MEK1 inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 21, 2006, Pages 5561-5566

  El Abdellaoui, Hassan ^a   Varaprasad, Chamakura V N S ^a   Barawkar, Dinesh ^a   Chakravarty, Subrata ^a   Maderna, Andreas ^a   Tam, Robert ^a   Chen, Huanming ^a   Allan, Matt ^a   Wu, Jim Z ^a   Appleby, Todd ^a   Yan, Shunqi ^a   Zhang, Weijian ^a   Lang, Stanley ^a   Yao, Nanhua ^a   Hamatake, Robert ^a   Hong, Zhi ^a  

^a Drug Discovery   (United States)

Author keywords

Allosteric inhibitors; Isothiazole carboxamidine; MEK inhibitor; MEK 1; MEK 2

Indexed keywords

5 [4 (2,5 DICHLOROPHENOXY)PHENYLAMINO] 3 HYDROXY N (2 HYDROXYPROPYL) ISOTHIAZOLE 4 CARBOXIMIDAMIDE; 5 AMINO 3 HYDROXY N (1 HYDROXYPROPANE 2 YL)ISOTHIAZOLE 4 CARBOXAMIDINE INHIBITOR; AMIDINE; AMINOPHENYL ETHER; ANILINE DERIVATIVE; ANTINEOPLASTIC AGENT; MITOGEN ACTIVATED PROTEIN KINASE 1 INHIBITOR; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; MITOGEN ACTIVATED PROTEIN KINASE KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE KINASE 2; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG DESIGN; DRUG DETERMINATION; DRUG EXPOSURE; DRUG POTENCY; DRUG SELECTIVITY; DRUG STRUCTURE; IN VITRO STUDY; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS; X RAY CRYSTALLOGRAPHY;

ALLOSTERIC REGULATION; AMIDINES; ANIMALS; MAP KINASE KINASE 1; MAP KINASE KINASE 2; RATS;

EID: 33748768253     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.08.048     Document Type: Article

References (32)

1. Seeger R., and Krebs E.G. FASEB J. 9 (1995) 726
2. Wallace E.M., Lyssikatos J.P., Yeh T., Winkler J.D., and Koch K. Curr. Top. Med. Chem. 5 (2005) 215
3. Robinson M.J., and Cobb M.H. Curr. Opin. Cell Biol. 9 (1997) 180
4. Chen Z., Soong-Hoon K., Barbosa S.A., Huynh T., and Tortolani K.J. Bioorg. Med. Chem. Lett. 16 (2006) 628
5. Kolch W. Biochem. J. 351 (2000) 289
6. Sivaraman V.S., and Wang H. J. Clin. Invest. 99 (1997) 1478
7. Dudley D.T., Pang L., Desker S.J., and Saltiel A.R. Proc. Natl. Acad. Sci. U.S.A. 92 (1995) 1478
8. Sebolt-Leopold J.S., Dudley D.T., Herrera R., Van Becelaere K., Wiland A., Gowan R.C., Tecle H., Barrett S.D., Bridges A., Przybranowski S., Leopold W.R., and Saltiel A.R. Proc. Natl. Acad. Sci. U.S.A. 5 (1999) 810
9. Duncia J.V., Santella J.B., Higley C.A., Pitts W.J., and Wityak J. Bioorg. Med. Chem. Lett. 8 (1998) 2839
10. Wityak J., Hobbs F.W., Gardner D.S., and Santella J.B. Bioorg. Med. Chem. Lett. 14 (2004) 1483
11. Zhong N., Wu B., Powell D., Wissner A., Floyd M.B., and Toral-Barza L. Bioorg. Med. Chem. Lett. 10 (2000) 2825
12. Zhang N., Wu B., Eudy N., Wang Y., Ye F., Powell D., Wissner A., and Feldberg L.R. Bioorg. Med. Chem. Lett. 11 (2001) 1407
13. Berger D., Dutia M., Powell D., Wu B., Wissner A., and Boschelli D.H. Bioorg. Med. Chem. Lett. 13 (2003) 3031
14. Boyle, F. T.; Gibson, K. H.; Poyser, J. P.; Turner, P. PTC Int. Appl. WO-2000068201, 2000.
15. Hennequin, L.; Froncois, A. PTC Int. Appl. WO-2004041811, 2004.
16. Ohren J.F., Chen H., Pavlosky A., Whitehead C., Zhang E., Kuffa P., yan C., McConnel P., Spessard C., and Banotai C. Nat. Struct. Mol. Biol. 12 (2004) 1192
17. Tecle, II. The development of Kinase Inhibitor with Unusual Mechanism of Action: CI-1040, A selective, non-ATP competitive MEK Inhibitor in the Clinic. IBC 2nd International Conference Protein Kinase: target Validation Drug Discovery and Clinical Development of kinase Therapeutics 2002, September 9-10.
18. Wallace E.M., Lyssikatos J.P., Yeh T., Winkler J.D., and Koch K. Curr. Top. Med. Chem. 5 (2005) 215
19. Han S., Zhou V., Pan S., Liu Y., Hornsby M., McMullan D., Klock H.E., Haugen J., Lesley S.A., Gray N., Caldwell J., and Gu X.-j. Bioorg. Med. Chem. Lett. 15 (2005) 5467
20. Zhang N., Wu B., Powell D., Wissner A., Toral-Barza L., Kovacs E.D., and Kohler C. Front. Biotechnol. Pharm. 1 (2000) 305
21. Mallon R., Feldberg L., Kim S., Collins K., Wojciechowicz D., Kohler C., Kovacs D., Discafani C., Zhang N., Wu B., Floyd B., Powell D., and Berger D. Mol. Cancer Ther. 3 (2004) 755 and references cited therein
22. Duncia J.V., Santella III J.B., Higley C.A., Pitts W.J., Wityak J., Frietze W.E., Rankin F.W., Sun J.-H., Earl R.A., Tabaka A.C., Teleha C.A., Blom K.F., Favata M.F., Manos E.J., Daulerio A.J., Stradley D.A., Horiuchi K., Copeland R.A., Scherle P.A., Trzaskos J.M., Magolda R.L., Trainor G.L., Wexler R.R., Hobbs F.W., and Olson R.E. Bioorg. Med. Chem. Lett. 8 (1998) 2839
23. Wityak J., Hobbs F.W., Gardner D.S., Santella III J.B., Petraitis J.J., Sun J.-H., Favata M.F., Daulerio A.J., Horiuchi K.Y., Copeland R.A., Scherle P.A., Jaffe B.D., Trzaskos J.M., Magolda R.L., Trainor G.L., and Duncia J.V. Bioorg. Med. Chem. Lett. 14 (2004) 1483
24. Levitzky A. Signal Transduction Therapy. In: Ke'ri Gy., and To'th I. (Eds). Molecular Pathomechanism and NewTrends in Drug Research (2003), Taylor & Francis, New York 55-58
25. Cohen M.H., Williams G.A., Sridhara R., Chen G., and Pazdur R. Ontogenesis 8 (2003) 303
26. Grunwald V., and Hidalgo M. Adv. Exp. Med. Biol. 532 (2003) 235
27. Harries M., and Smith I. Endocr. Relat. Cancer 9 (2002) 75
28. Dancey J., and Sausville E.A. Nat. Rev. Drug Disc. 2 (2003) 296
29. Ferrara N., Hillan K.J., Gerber H.P., and Novotny W. Nat. Rev. Drug Disc. 3 (2004) 391
30. Simon F. Nature 437 (2005) 942
31. Varaprasad C.V.N.S., Barawkar D., El Abdellaoui H., Chakravarty S., Allan M., Chen H., Zhang W., Wu J., Tam R., Hamatake R., Lang S., and Hong Z. Bioorg. Med. Chem. Lett. 16 (2006) 3975
32. 50 assay, kinase profiling, and kinetics, please see Supplementary data.