Identification of PDE4B Over 4D subtype-selective inhibitors revealing an unprecedented binding mode

Bioorganic and Medicinal Chemistry

Volumn 17, Issue 14, 2009, Pages 5336-5341

  Kranz, Michael ^a   Wall, Michael ^a   Evans, Brian ^a   Miah, Afjal ^a   Ballantine, Stuart ^a   Delves, Chris ^a   Dombroski, Brian ^a   Gross, Jeffrey ^a   Schneck, Jessica ^a   Villa, James P ^a   Neu, Margarete ^a   Somers, Don O ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

Author keywords

Induced fit; Lead optimisation; Ligand docking; SAR

Indexed keywords

2 AMINO 6 METHYL 4,5,6,7 TETRAHYDRO 1 BENZOTHIOPHENE 3 CARBOXAMIDE; 6 METHYL 2 [[(2 NITROPHENYL)CARBONYL]AMINO] 4,5,6,7 TETRAHYDRO 1 BENZOTHIOPHENE 3 CARBOXAMIDE; GLUTAMINE; LIGAND; PHOSPHODIESTERASE 4B; PHOSPHODIESTERASE 4B INHIBITOR; PHOSPHODIESTERASE 4D INHIBITOR; PHOSPHODIESTERASE IV; PHOSPHODIESTERASE IV INHIBITOR; TETRAHYDROBENZOTHIOPHENE; UNCLASSIFIED DRUG;

ARTICLE; CARBOXY TERMINAL SEQUENCE; CRYSTAL STRUCTURE; DRUG BINDING SITE; DRUG CONFORMATION; DRUG DESIGN; DRUG POTENCY; DRUG SELECTIVITY; INFLAMMATORY CELL; LIGAND BINDING; MOLECULAR DOCKING; STRUCTURE ACTIVITY RELATION; X RAY CRYSTALLOGRAPHY;

AMINO ACID SEQUENCE; BINDING SITES; CRYSTALLOGRAPHY, X-RAY; CYCLIC NUCLEOTIDE PHOSPHODIESTERASES, TYPE 4; HUMANS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; MUTATION; PROTEIN BINDING; PROTEIN CONFORMATION; STRUCTURE-ACTIVITY RELATIONSHIP; THIOPHENES;

EID: 67650072396     PISSN: 09680896     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmc.2009.03.061     Document Type: Article

References (23)

1. Cheung W.Y. Biochemistry 6 (1967) 1079
2. Schwabe U., Miyake M., Ohga Y., and Daly J. Mol. Pharmacol. 12 (1976) 900
3. Dastidar S.G., Rajagopal D., and Ray A. Curr. Opin. Invest. Drugs 85 (2007) 364
4. Jin S.-L.C., Lan L., Zoudilova M., and Conti M. J. Immun. 175 (2005) 1523
5. Robichaud A., Stamatiou P.B., Jin S.-L.C., Lachance N., MacDonald D., Laliberte F., Liu S., Huang Z., Conti M., and Chan C.-C. J. Clin. Invest. 110 (2002) 1045
6. Zhang K.Y.J., Card G.L., Suzuki Y., Artis D.R., Fong D., Gillette S., Hsieh D., Neiman J., West B.L., Zhang C., Milburn M.V., Kim S.-H., Schlessinger J., and Bollag G. Mol. Cell 15 (2004) 279
7. 50 values. Average standard deviations are for PDE4B = 0.10 and PDE4D = 0.11.
8. Allen F.H. Acta Crystallogr., Sect. B 58 (2002) 380
9. Lee M.E., Markowitz J., Lee J.-O., and Lee H. FEBS Lett. 530 (2002) 53
10. Allen F.H., Bird C.M., Rowland R.S., and Raithby P.R. Acta Crystallogr. Sect. B 53 (1997) 696
11. Mcmartin C., and Bohacek R.S. J. Comp. Aided Mol. Des. 11 (1997) 333
12. Card G.L., England B.P., Suzuki Y., Fong D., Powell B., Lee B., Luu C., Tabrizizad M., Gillette S., Ibrahim P.N., Artis D.R., Bollag G., Milburn M.V., Kim S.-H., Schlessinger J., and Zhang K.Y.J. Structure 12 (2004) 2233
13. Gewald K., and Schael J. J. Prakt. Chem. 315 (1973) 39
14. Houslay M.D., and Adams D.R. Biochem. J. 370 (2003) 1
15. McLaughlin M.M., Cieslinski L.B., Burman M., Torphy T.J., and Livi G.P. J. Biol. Chem. 268 (1993) 6470
16. Xu R.X., Hassell A.M., Vanderwall D., Lambert M.H., Holmes W.D., Luther M.A., Rocque W.J., Milburn M.V., Zhao Y., Ke H., and Nolte R.T. Science 288 (2000) 1822
17. Manuscript in preparation.
18. Wang H., Peng M.-S., Chen Y., Robinson H., Houslay M.D., Cai J., and Ke H. Biochem. J. 408 (2007) 193
19. Rocque W.J., Holmes W.D., Patel I.R., Dougherty R.W., Ittoop O., Overton L., Hoffman C.R., Wisely G.B., Willard D.H., and Luther M.A. Protein Exp. Purif. 9 (1997) 191
20. Leslie, A. G. W., Joint CCP4 + ESF-EAMCB Newsletter on Protein Crystallography, 1992, No. 26.
21. Bailey S. Acta Crystallogr. Sect. D 50 (1994) 760
22. Storoni L.C., McCoy A.J., and Read R.J. Acta Crystallogr. Sect. D 60 (2004) 432
23. Murshudov G.N., Vagin A.A., and Dodson E.J. Acta Crystallogr. Sect. D 53 (1997) 240