NMR methods in fragment based drug discovery

Lim, Jongsoo

doi:10.6564/JKMRS.2015.19.3.132

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NMR methods in fragment based drug discovery

Journal title : Journal of the Korean Magnetic Resonance Society
Volume 19, Issue 3, 2015, pp.132-136
Publisher : Korean Magnetic Resonance Society
DOI : 10.6564/JKMRS.2015.19.3.132

Title & Authors

NMR methods in fragment based drug discovery
Lim, Jongsoo;

Abstract

Nuclear magnetic resonance (NMR) spectroscopy, owing to its ability to provide atomic level information on molecular structure, dynamics and interaction, has become one of the most powerful methods in early drug discovery where hit finding and hit-to-lead generation are mainly pursued. In recent years, drug discovery programs originating from the fragment-based drug discovery (FBDD) strategies have been widely incorporated into academia and industry in which a wide variety of NMR methods become an indispensable arsenal to elucidate the binding of small molecules onto bimolecular targets. In this review, I briefly describe FBDD and introduce NMR methods mainly used in FBDD campaigns of my company. In addition, quality control of fragment library and practical NMR methods in industrial aspect are discussed shortly.

Keywords

FBDD;HTS;NMR;Fragment library quality control;

Language

English

Cited by

References

R. Macarron, M. N. Banks, D. Bojanic, D. J. Burns, D. A. Cirovic, T. Garyantes, D. V. Green, R. P. Hertzberg, W. P. Janzen, J. W. Paslay, U. Schopfer, and G. S. Sittampalam, Nat. Rev. Drug Discov. 10, 3 (2011)

S. B. Shuker, P. J. Hajduk, R. P. Meadows, and S. W. Fesik, Science 274, 5292 (1996)

W. P. Jencks, Proc. Natl. Acad. Sci. U S A. 78, 7 (1981)

C. A. Lipinski, F. Lombardo, B. W. Dominy, and P. J. Feeney, Adv. Drug. Deliv. Rev. 46, 1-3 (2001)

T. sMaurer, L. S. Garrenton, A. Oh, K. Pitts, D. J. Anderson, N. J. Skelton, B. P. Fauber, B. Pan, S. Malek, D. Stokoe, M. J. Ludlam, K. K. Bowman, J. Wu, A. M. Giannetti, M. A. Starovasnik, I. Mellman, P. K. Jackson, J. Rudolph, W. Wang, and G. Fang, Proc. Natl. Acad. Sci. U S A. 109, 14 (2012)

Q. Sun, J. P. Burke, J. Phan, M. C. Burns, E. T. Olejniczak, A. G. Waterson, T. Lee, O. W. Rossanese, and S. W. Fesik, Angew. Chem. Int. Ed. Engl. 51, 25 (2012)

H. Chen, X. Zhou, A. Wang, Y. Zheng, Y. Gao, and J. Zhou, Drug Discov. Today 20, 1 (2015)

M. Pellecchia, D. S. Sem, and K. Wuthrich, Nat. Rev. Drug Discov. 1, 3 (2002)

M. Mayer and B. Meyer, Angewandte Chemie International Edition 38, 12 (1999)

10.

C. Dalvit, P. Pevarello, M. Tato, M. Veronesi, A. Vulpetti, and M. Sundstrom, J.Biomol.NMR 18, 1 (2000)

11.

J. B. Jordan, L. Poppe, X. Xia, A. C. Cheng, Y. Sun, K. Michelsen, H. Eastwood, P. D. Schnier, and T. Nixey, W. Zhong, J.Med.Chem. 55, 2 (2012)

12.

C. Dalvit, M. Flocco, M. Veronesi, and B. J. Stockman, Comb.Chem.High Throughput Screen 5, 8 (2002)

13.

L. Oster, S. Tapani, Y. Xue, and H. Kack, Drug Discov.Today 20, 9 (2015)

14.

C. Aguirre, T. t. Brink, J.-F. Guichou, O. Cala, and I. Krimm, PLoS One 9, 7 (2014)

15.

M. Mayer and B. Meyer, Journal of the American Chemical Society 123, 25 (2001)

16.

J. Baell and M. A. Walters, Nature 513, 7519 (2014)

17.

S. R. Laplante, R. J. Carson, J. R. Gillard, N. Aubry, R. Coulombe, S. Bordeleau, P. R. Bonneau, M. Little, J. A. Omeara, and P. L. Beaulieu, J. Med. Chem. (2013)

18.

D. M. Dias and A. Ciulli, Prog. Biophys. Mol. Biol. 116, 2-3 (2014)

19.

J. Y. Guan, P. H. Keizers, W. M. Liu, F. Lohr, S. P. Skinner, E. A. Heeneman, H. Schwalbe, M. Ubbink, and G. Siegal, J. Am. Chem. Soc. 135, 15 (2013)

20.

C. Aguirre, T. ten Brink, O. Walker, F. Guilliere, D. Davesne, and I. Krimm, PLoS One 8, 5 (2013)