Fragment-based drug design capitalizes on the modular binding of low-molecular-weight, low-affinity ligands. However, the deconstruction of lead-like inhibitors into putative fragments reveals the surprising complexity of dealing with low-affinity leads, thereby challenging oversimplification of these leads and highlighting the richness of their chemical diversity and molecular recognition.
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References
Erlanson, D.A., McDowell, R.S. & O'Brien, T. J. Med. Chem. 47, 3463–3482 (2004).
Hajduk, P.J., Huth, J.R. & Sun, C. Methods and Principles in Medicinal Chemistry 34, 181–192 (2006).
Hajduk, P.J., Huth, J.R. & Fesik, S.W. J. Med. Chem. 48, 2518–2525 (2005).
Babaoglu, K. & Shoichet, B.K. Nat. Chem. Biol. 2, 720–723 (2006).
Hann, M.M., Leach, A.R. & Harper, G. J. Chem. Inf. Comput. Sci. 41, 856–864 (2001).
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Hajduk, P. Puzzling through fragment-based drug design. Nat Chem Biol 2, 658–659 (2006). https://doi.org/10.1038/nchembio1206-658
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DOI: https://doi.org/10.1038/nchembio1206-658
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