Electron density guided fragment-based lead discovery of ketohexokinase inhibitors

…, BA Tounge, FA Lewandowski, GT Struble…

Index: Gibbs, Alan C.; Abad, Marta C.; Zhang, Xuqing; Tounge, Brett A.; Lewandowski, Francis A.; Struble, Geoffrey T.; Sun, Weimei; Sui, Zhihua; Kuo, Lawrence C. Journal of Medicinal Chemistry, 2010 , vol. 53, # 22 p. 7979 - 7991

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Citation Number: 20

Abstract

A fragment-based drug design paradigm has been successfully applied in the discovery of lead series of ketohexokinase inhibitors. The paradigm consists of three iterations of design, synthesis, and X-ray crystallographic screening to progress low molecular weight fragments to leadlike compounds. Applying electron density of fragments within the protein binding site as defined by X-ray crystallography, one can generate target specific leads without the ...