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Computationally Guided Design of Two Novel Soluble Epoxide Hydrolase Inhibitors

Dere, E. C.; Chu, S. S.; Ortega, T.; Huang, P.; Siegel, J. B.

2022-09-13 biochemistry
10.1101/2022.09.13.507703 bioRxiv
Show abstract

The enzyme soluble epoxide hydrolase (sEH) has been found to play a role in many ailments such as inflammation, pain, renal function, pulmonary function, hypertension, and diabetes. Multiple sEH inhibitors have been developed to reduce the adverse effects of the ailments. Due to high inhibitory concentrations, there is urgent need for developing improved sEH inhibitors. In this study, two novel sEH inhibitors were designed via computational bioisosteric replacement and chemical intuition with the goal of increasing binding affinity, which can potentially decrease inhibitory concentration. The new drug candidates were found to have improved binding properties compared to existing drugs.

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