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Computer-Aided Fragment Growing Strategies to Design Dual Inhibitors of Soluble Epoxide Hydrolase and LTA4 Hydrolase.

ABSTRACT: 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.

SUBMITTER: Hefke L

PROVIDER: S-EPMC7294724 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Computer-Aided Fragment Growing Strategies to Design Dual Inhibitors of Soluble Epoxide Hydrolase and LTA4 Hydrolase.

Hefke Lena L Hiesinger Kerstin K Zhu W Felix WF Kramer Jan S JS Proschak Ewgenij E

ACS medicinal chemistry letters 20200408 6

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 struc ...[more]

PMID: 32551007

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