1. Computer-Aided Fragment Growing Strategies to Design Dual Inhibitors of Soluble Epoxide Hydrolase and LTA4 Hydrolase
- Author
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Lena Hefke, W. Felix Zhu, Ewgenij Proschak, Kerstin Hiesinger, Jan S. Kramer, and Publica
- Subjects
Epoxide hydrolase 2 ,010405 organic chemistry ,Drug discovery ,Chemistry ,fungi ,Organic Chemistry ,Rational design ,Computational biology ,DUAL (cognitive architecture) ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Fragment (logic) ,LTA4 hydrolase ,Drug Discovery ,Polypharmacology - Abstract
[Image: see text] Multitarget ligands are interesting candidates for drug discovery and development due to improved safety and efficacy. However, rational design and optimization of multitarget ligands is tedious because affinity optimization for two or more targets has to be performed simultaneously. In this study, we demonstrate that, given a molecular fragment, which binds to two targets of interest, computer-aided fragment growing can be applied to optimize compound potency, relying on either ligand- or structure-derived information. This methodology is applied to the design of dual inhibitors of soluble epoxide hydrolase and leukotriene A4 hydrolase.
- Published
- 2020