ArticleBioorganic & medicinal chemistry letters2018
Identification and optimization of soluble epoxide hydrolase inhibitors with dual potency towards fatty acid amide hydrolase.
Article in Bioorganic & medicinal chemistry letters, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 36 citations in OpenAlex.
- Article
- Hepatic Transcriptome and Its Regulation Following Soluble Epoxide Hydrolase Inhibition in Alcohol-Associated Liver Disease.The American journal of pathology · 2024Article
- 4-Phenyl-thiazole-based dual inhibitors of fatty acid amide hydrolase and soluble epoxide hydrolase do not alleviate orofacial inflammatory pain in female rats.BBA advances · 2024Article
- Repositioning of Quinazolinedione-Based Compounds on Soluble Epoxide Hydrolase (sEH) through 3D Structure-Based Pharmacophore Model-Driven Investigation.Molecules (Basel, Switzerland) · 2022Article
- Phthalate's multiple hormonal effects and their supplementary dietary regulation scheme of health risks for children.Environmental science and pollution research international · 2022Article
- Polypharmacological Approaches for CNS Diseases: Focus on Endocannabinoid Degradation Inhibition.Cells · 2022Review
- Further exploration of the structure-activity relationship of dual soluble epoxide hydrolase/fatty acid amide hydrolase inhibitors.Bioorganic & medicinal chemistry · 2021Article
- Discovery of Soluble Epoxide Hydrolase Inhibitors from Chemical Synthesis and Natural Products.Journal of medicinal chemistry · 2021Review
- Small Molecule Soluble Epoxide Hydrolase Inhibitors in Multitarget and Combination Therapies for Inflammation and Cancer.Molecules (Basel, Switzerland) · 2020Review
- Design of Dual Inhibitors of Soluble Epoxide Hydrolase and LTAACS medicinal chemistry letters · 2020Article
- Imidazolidine-2,4,5- and pirimidine-2,4,6-triones - New primary pharmacophore for soluble epoxide hydrolase inhibitors with enhanced water solubility.Bioorganic & medicinal chemistry letters · 2020Article
- Epoxy Fatty Acids Are Promising Targets for Treatment of Pain, Cardiovascular Disease and Other Indications Characterized by Mitochondrial Dysfunction, Endoplasmic Stress and Inflammation.Advances in experimental medicine and biology · 2020Review
- The molecular structure of an epoxide hydrolase from Trichoderma reesei in complex with urea or amide-based inhibitors.International journal of biological macromolecules · 2019Article
- Role of epoxy-fatty acids and epoxide hydrolases in the pathology of neuro-inflammation.Biochimie · 2019Review
- Development of multitarget agents possessing soluble epoxide hydrolase inhibitory activity.Prostaglandins & other lipid mediators · 2019Review
- Design and Potency of Dual Soluble Epoxide Hydrolase/Fatty Acid Amide Hydrolase Inhibitors.ACS omega · 2018Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Multi-target inhibitors have become increasing popular as a means to leverage the advantages of poly-pharmacology while simplifying drug delivery. Here, we describe dual inhibitors for soluble epoxide hydrolase (sEH) and fatty acid amide hydrolase (FAAH), two targets known to synergize when treating inflammatory and neuropathic pain. The structure activity relationship (SAR) study described herein initially started with t-TUCB (trans-4-[4-(3-trifluoromethoxyphenyl-l-ureido)-cyclohexyloxy]-benzoic acid), a potent sEH inhibitor that was previously shown to weakly inhibit FAAH. Inhibitors with a 6-fold increase of FAAH potency while maintaining high sEH potency were developed by optimization. Interestingly, compared to most FAAH inhibitors that inhibit through time-dependent covalent modification, t-TUCB and related compounds appear to inhibit FAAH through a time-independent, competitive mechanism. These inhibitors are selective for FAAH over other serine hydrolases. In addition, FAAH inhibition by t-TUCB appears to be higher in human FAAH over other species; however, the new dual sEH/FAAH inhibitors have improved cross-species potency. These dual inhibitors may be useful for future studies in understanding the therapeutic application of dual sEH/FAAH inhibition.
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Registered trials
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