Discovery of a novel family of CDK inhibitors with the program LIDAEUS: Structural basis for ligand-induced disordering of the activation loop

Structure

Volumn 11, Issue 4, 2003, Pages 399-410

  Wu, Su Ying ^a,b   McNae, Iain ^a,b   Kontopidis, George ^b   McClue, Steven J ^b   McInnes, Campbell ^b   Stewart, Kevin J ^b   Wang, Shudong ^b   Zheleva, Daniella I ^b   Marriage, Howard ^b   Lane, David P ^b   Taylor, Paul ^a,b   Fischer, Peter M ^b   Walkinshaw, Malcolm D ^a,b  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

^b CYCLACEL LTD   (United Kingdom)

Author keywords

Automated docking; CDK2; Drug design; Ligand binding

Indexed keywords

ADENOSINE TRIPHOSPHATE; CD 09763; CD 09767; CD 09770; CYCLIN D1; CYCLIN DEPENDENT KINASE 2; CYCLIN DEPENDENT KINASE INHIBITOR; CYCLIN E; FLAVOPIRIDOL; INDIRUBIN; OXINDOLE; PURVALANOL B; PYRIDINYLUREA; PYRIMIDINE DERIVATIVE; ROSCOVITINE; STAUROSPORINE; UNCLASSIFIED DRUG; UREA DERIVATIVE;

AMINO ACID SEQUENCE; ARTICLE; CANCER CELL CULTURE; CELL PROLIFERATION; COMPUTER PROGRAM; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; CORRELATION ANALYSIS; DRUG POTENCY; DRUG SCREENING; ENZYME ACTIVE SITE; ENZYME ASSAY; HUMAN; HUMAN CELL; HYDROGEN BOND; LIGAND BINDING; PHARMACOPHORE; PRIORITY JOURNAL; PROTEIN FAMILY; PROTEIN STRUCTURE; X RAY CRYSTALLOGRAPHY;

EID: 0346214475     PISSN: 09692126     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0969-2126(03)00060-1     Document Type: Article

References (46)

1. Fischer P.M. Recent advances and new directions in the discovery and development of cyclin-dependent kinase inhibitors. Curr. Opin. Drug Discov. Dev. 4:2001;623-634.
2. Malumbres M., Barbacid M. To cycle or not to cycle. a critical decision in cancer Nat. Rev. Cancer. 1:2001;222-231.
3. Cohen P. Protein kinases - the major drug targets of the twenty-first century? Nat. Rev. Drug Discov. 1:2002;309-315.
4. Endicott J.A., Noble M.E.M., Tucker J.A. Cyclin-dependent kinases. inhibition and substrate recognition Curr. Opin. Struct. Biol. 9:1999;738-744.
5. Sausville E.A. Complexities in the development of cyclin-dependent kinase inhibitor drugs. Trends Mol. Med. 8:2002;S32-S37.
6. Hoessel R., Leclerc S., Endicott J.A., Nobel M.E.M., Lawrie A., Tunnah P., Leost M., Damiens E., Marie D., Marko D.et al. Indirubin, the active constituent of a Chinese antileukaemia medicine, inhibits cyclin-dependent kinases. Nat. Cell Biol. 1:1999;60-67.
7. Wang S., McClue S.J., Ferguson J.R., Hull J.D., Stokes S., Parsons S., Westwood R., Fischer P.M. Synthesis and configuration of the cyclin-dependent kinase inhibitor roscovitine and its enantiomer. Tetrahedron Asymmetry. 12:2001;2891-2894.
8. Newell D.R. Review of clinical trials with cell cycle based strategies. Clin. Cancer Res. Suppl. 7:2001;3822s.
9. Burkhard P., Taylor P., Walkinshaw M.D. An example of a protein ligand found by database mining. description of the docking method and its verification by a 2.3 Å X-ray structure of a thrombin-ligand complex J. Mol. Biol. 277:1998;449-466.
10. Walkinshaw M.D., Floersheim P. Hydrophilicity of proteins and DNA. J. Mol. Struct. 237:1990;63-73.
11. Janin J. Elusive affinities. Proteins Struct. Funct. Genet. 21:1995;30-39.
12. Fischer P.M., Lane D.P. Inhibitors of cyclin-dependent kinases as anti-cancer therapeutics. Curr. Med. Chem. 7:2000;1213-1245.
13. Wang S., Blake D., Clarke R., Duff S., McClue S.J., McInnes C., Melville J., Stewart K., Taylor P., Westwood R.et al. 4-Heteroaryl-2-phenylamino-pyrimidines, a new class of CDK2 inhibitors. discovery, optimisation, and anti-proliferative activity in vitro and in vivo Proc. Am. Assoc. Cancer Res. 43:2002;4202.
14. Schulze-Gahmen U., De Bondt H.L., Kim S.H. High-resolution crystal structures of human cyclin-dependent kinase 2 with and without ATP. bound waters and natural ligand as guides for inhibitor design J. Med. Chem. 39:1996;4540-4546.
15. Hardcastle I.R., Golding B.T., Griffin R.J. Designing inhibitors of cyclin-dependent kinases. Annu. Rev. Pharmacol. Toxicol. 42:2002;325-348.
16. Kim K.S., Sack J.S., Tokarski J.S., Qian L., Chao S.T., Leith L., Kelly Y.F., Misra R.N., Hunt J.T., Kimball S.D.et al. Thio- and oxoflavopiridols, cyclin-dependent kinase 1-selective inhibitors. synthesis and biological effects J. Med. Chem. 43:2000;4126-4134.
17. Gray N.S., Wodicka L., Thunissen A.-M.W.H., Norman T.C., Kwon S., Espinoza F.H., Morgan D.O., Barnes G., LeClerc S., Meijer L.et al. Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors. Science. 281:1998;533-538.
18. Dreyer M.K., Borcherding D.R., Dumont J.A., Peet N.P., Tsay J.T., Wright P.S., Bitonti A.J., Shen J., Kim S.-H. Crystal structure of human cyclin-dependent kinase 2 in complex with the adenine-derived inhibitor H717. J. Med. Chem. 44:2001;524-530.
19. De Azevedo W.F., Leclerc S., Meijer L., Havlicek L., Strnad M., Kim S.H. Inhibition of cyclin-dependent kinases by purine analogues. crystal structure of human cdk2 complexed with roscovitine Eur. J. Biochem. 243:1997;518-526.
20. Legraverend M., Tunnah P., Noble M., Ducrot P., Ludwig O., Grierson D.S., Leost M., Meijer L., Endicott J. Cyclin-dependent kinase inhibition by new C-2 alynylated purine derivatives and molecular structure of a CDK2-inhibitor complex. J. Med. Chem. 43:2000;1282-1292.
21. Arris C.E., Boyle F.T., Calvert A.H., Curtin N.J., Endicott J.E., Garman E.F., Gibson A.E., Golding B.T., Grant S., Griffin R.J.et al. Identification of novel purine and pyrimidine cyclin-dependent kinase inhibitors with distinct molecular interactions and tumor cell growth inhibition profiles. J. Med. Chem. 43:2000;2797-2804.
22. Bramson H.N., Corona J., Davis S.T., Dickerson S.H., Edelstein M., Frye S.V., Gampe R.T. Jr., Harris P.A., Hassell A., Holmes W.D.et al. Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2). design, synthesis, enzymatic activities, and X-ray crystallographic analysis J. Med. Chem. 44:2001;4339-4358.
23. Barvian M., Boschelli D.H., Crossrow J., Dobrusin E., Fattaey A., Fritsch A., Fry D., Harvey P., Keller P., Garrett M.et al. Pyrido[2,3-d]pyrimidin-7-one inhibitors of cyclin-dependent kinases. J. Med. Chem. 43:2000;4606-4616.
24. Laskowski R.A., Thornton J.M., Humblet C., Singh J. X-site. use of empirically derived atomic packing preferences to identify favorable interaction regions in the binding sites of proteins J. Mol. Biol. 259:1996;175-201.
25. Fischer, P.M., and Wang, S. (2001). 2-Substituted 4-heteroaryl-pyrimidines and their use in the treatment of proliferative disorders. PCT International Patent Application Publication WO 2001072745, Cyclacel Limited, UK.
26. Brown N.R., Noble M.E.M., Lawrie A.M., Morris M.C., Tunnah P., Divita G., Johnson L.N., Endicott J.A. Effects of phosphorylation of threonine 160 on cyclin-dependent kinase 2 structure and activity. J. Biol. Chem. 274:1999;8746-8756.
27. Pavletich N.P. Mechanisms of cyclin-dependent kinase regulation. structures of Cdks, their cyclin activators, and Cip and INK4 inhibitors J. Mol. Biol. 287:1999;821-828.
28. Schindler T., Bornmann W., Pellicena P., Miller W.T., Clarkson B., Kuriyan J. Structural mechanism for STI-571 inhibition of Abelson tyrosine kinase. Science. 289:2000;1938-1942.
29. Huse M., Kuriyan J. The conformational plasticity of protein kinases. Cell. 109:2002;275-282.
30. Davies T.G., Tunnah P., Meijer L., Marko D., Eisenbrand G., Endicott J.A., Noble M.E.M. Inhibitor binding to active and inactive CDK2. the crystal structure of CDK2-cyclin A/indirubin-5-sulphonate Structure. 9:2001;389-397.
31. Rosenblatt J., De Bondt H., Jancarik J., Morgan D.O., Kim S.H. Purification and crystallization of human cyclin-dependent kinase 2. J. Mol. Biol. 230:1993;1317-1319.
32. Otwinowski Z., Minor W. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276:1997;307-326.
33. Lamzin V.S., Wilson K.S. Automated refinement for protein crystallography. Methods Enzymol. 277:1997;269-305.
34. Brunger A.T., Adams P.D., Clore G.M., DeLano W.L., Gros P., Grosse-Kunstleve R.W., Jiang J.S., Kuszewski J., Nilges M., Pannu N.S.et al. Crystallography and NMR system. a new software suite for macromolecular structure determination Acta Crystallogr. D. 54:1998;905-921.
35. Murshudov G.N., Vagin A.A., Dodson E.J. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D53:1997;240-255.
36. Sheldrick G.M., Schneider T.R. Shelxl. high-resolution refinement Methods Enzymol. 277:1997;319-343.
37. Jones T.A., Zou J.Y., Cowan S.W., Kjeldgaard M. Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr. A47:1991;110-119.
38. Bredereck H., Effenberger F., Botsch H. Acid amide reactions. XLV. Reactivity of formamidines, dimethylformamide diethyl acetal (amide acetal), and bis(dimethylamino)methoxymethane (aminal ester). Chem. Ber. 97:1964;3397-3406.
39. Zimmermann J., Caravatti G., Mett H., Meyer T., Müller M., Lydon N.B., Fabbro D. Phenylamino-pyrimidine (PAP) derivatives. a new class of potent and selective inhibitors of protein kinase C (PKC) Arch. Pharm. 329:1996;371-376.
40. Davies S.P., Reddy H., Caivano M., Cohen P. Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem. J. 351:2000;95-105.
41. Haselsberger K., Peterson D.C., Thomas D.G., Darling J.L. Assay of anticancer drugs in tissue culture. comparison of a tetrazolium-based assay and a protein binding dye assay in short-term cultures derived from human malignant glioma Anticancer Drugs. 7:1996;331-338.
42. Shewchuk L., Hassell A., Wisely B., Rocque W., Holmes W., Veal J., Kuyper L.F. Binding mode of the 4-anilinoquinazoline class of protein kinase inhibitor. X-ray crystallographic studies of 4-anilinoquinazolines bound to cyclin-dependent kinase 2 and p38 kinase J. Med. Chem. 43:2000;133-138.
43. De Azevedo W.F. Jr., Mueller-Dieckmann H.J., Schulze-Gahmen U., Worland P.J., Sausville E., Kim S.H. Structural basis for specificity and potency of a flavonoid inhibitor of human CDK2, a cell cycle kinase. Proc. Natl. Acad. Sci. USA. 93:1996;2735-2740.
44. Ikuta M., Kamata K., Fukasawa K., Honma T., Machida T., Hirai H., Suzuki-Takahashi I., Hayama T., Nishimura S. Crystallographic approach to identification of cyclin-dependent kinase 4 (CDK4)-specific inhibitors by using CDK4 mimic CDK2 protein. J. Biol. Chem. 276:2001;27548-27554.
45. Lawrie A.M., Noble M.E., Tunnah P., Brown N.R., Johnson L.N., Endicott J.A. Protein kinase inhibition by staurosporine revealed in details of the molecular interaction with CDK2. Nat. Struct. Biol. 4:1997;796-801.
46. Meijer L., Thunnissen A.-M.W.H., White A.W., Garnier M., Nikolic M., Tsai L.-H., Walter J., Cleverley K.E., Salinas P.C., Wu Y.-Z.et al. Inhibition of cyclin-dependent kinases, GSK-3β and CK1 by hymenialdisine, a marine sponge constituent. Chem. Biol. 7:2000;51-63.