7A7G

Soluble epoxide hydrolase in complex with TK90

Summary for 7A7G

• Entry DOI: 10.2210/pdb7a7g/pdb
• Descriptor: Bifunctional epoxide hydrolase 2, (2~{R})-2-[[4-[[4-methoxy-2-(trifluoromethyl)phenyl]methylcarbamoyl]phenyl]methyl]butanoic acid (3 entities in total)
• Functional Keywords: complex, structural genomics, structural genomics consortium, sgc, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 80115.86

Authors

Ni, X.,Kramer, J.S.,Kirchner, T.,Proschak, E.,Chaikuad, A.,Knapp, S.,Structural Genomics Consortium (SGC) (deposition date: 2020-08-28, release date: 2021-08-04, Last modification date: 2024-01-31)

Primary citation

Hartmann, M.,Bibli, S.I.,Tews, D.,Ni, X.,Kircher, T.,Kramer, J.S.,Kilu, W.,Heering, J.,Hernandez-Olmos, V.,Weizel, L.,Scriba, G.K.E.,Krait, S.,Knapp, S.,Chaikuad, A.,Merk, D.,Fleming, I.,Fischer-Posovszky, P.,Proschak, E.
Combined Cardioprotective and Adipocyte Browning Effects Promoted by the Eutomer of Dual sEH/PPAR gamma Modulator.
J.Med.Chem., 64:2815-2828, 2021

PubMed Abstract: The metabolic syndrome (MetS) is a constellation of cardiovascular and metabolic symptoms involving insulin resistance, steatohepatitis, obesity, hypertension, and heart disease, and patients suffering from MetS often require polypharmaceutical treatment. PPARγ agonists are highly effective oral antidiabetics with great potential in MetS, which promote adipocyte browning and insulin sensitization. However, the application of PPARγ agonists in clinics is restricted by potential cardiovascular adverse events. We have previously demonstrated that the racemic dual sEH/PPARγ modulator RB394 () simultaneously improves all risk factors of MetS in vivo. In this study, we identify and characterize the eutomer of . We provide structural rationale for molecular recognition of the eutomer. Furthermore, we could show that the dual sEH/PPARγ modulator is able to promote adipocyte browning and simultaneously exhibits cardioprotective activity which underlines its exciting potential in treatment of MetS.

PubMed: 33620196
DOI: 10.1021/acs.jmedchem.0c02063

Experimental method

X-RAY DIFFRACTION (2.4 Å)