| Title : Fragment-Based Discovery of Fenamic Acids as Pan-Species Inhibitors of the Soluble Epoxide Hydrolase Phosphatase Domain - Zhu_2026_ACS.Chem.Biol_21_2053 |
| Author(s) : Zhu WF , Feugray G , Brunst S , Messaoudi H , Yang M , Martinez-Conde N , Kramer A , Weizel L , Ehrler JMH , Kramer JS , Kaiser A , Al-Tarrass M , Pereira T , Valet M , Brunel V , Schubert-Zsilavecz M , Knapp S , Lillich FF , Hernandez-Olmos V , Duflot T , Hiesinger K , Qian H , Proschak A , Bellien J , Proschak E |
| Ref : ACS Chemical Biology , 21 :2053 , 2026 |
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Abstract :
Targeting the N-terminal phosphatase domain of soluble epoxide hydrolase (sEH) could potentially represent a pharmacological strategy for treatment of cardiometabolic diseases. However, development of chemical tools to investigate the therapeutic potential of sEH phosphatase (sEH-P) inhibition has proven challenging due to varying activities between different species isoforms and lack of selectivity toward the C-terminal hydrolase domain, which exhibits the epoxide hydrolase activity (sEH-H). Herein, we describe the fragment-based discovery of FZ581 (49), an sEH-P inhibitor against human, rat, and mouse isoforms. In vivo studies with this compound in mice and rats demonstrated a significant increase of main sEH-P substrate levels without affecting plasma levels of sEH-H substrates. Altogether, we provide a pan-species sEH-P inhibitor to study the pharmacotherapeutic potential of sEH-P inhibition. |
| PubMedSearch : Zhu_2026_ACS.Chem.Biol_21_2053 |
| PubMedID: 42631699 |
Zhu WF, Feugray G, Brunst S, Messaoudi H, Yang M, Martinez-Conde N, Kramer A, Weizel L, Ehrler JMH, Kramer JS, Kaiser A, Al-Tarrass M, Pereira T, Valet M, Brunel V, Schubert-Zsilavecz M, Knapp S, Lillich FF, Hernandez-Olmos V, Duflot T, Hiesinger K, Qian H, Proschak A, Bellien J, Proschak E (2026)
Fragment-Based Discovery of Fenamic Acids as Pan-Species Inhibitors of the Soluble Epoxide Hydrolase Phosphatase Domain
ACS Chemical Biology
21 :2053
Zhu WF, Feugray G, Brunst S, Messaoudi H, Yang M, Martinez-Conde N, Kramer A, Weizel L, Ehrler JMH, Kramer JS, Kaiser A, Al-Tarrass M, Pereira T, Valet M, Brunel V, Schubert-Zsilavecz M, Knapp S, Lillich FF, Hernandez-Olmos V, Duflot T, Hiesinger K, Qian H, Proschak A, Bellien J, Proschak E (2026)
ACS Chemical Biology
21 :2053