SWE101   

GtoPdb Ligand ID: 10494

Synonyms: compound 22b [PMID: 31436984]
Compound class: Synthetic organic
Comment: SWE101 is a soluble epoxide hydrolase (sEH; EPHX2) inhibitor that selectively, and competitively targets the enzyme's phosphatase activity [2]. Its structure was developed from the scaffold of the NSAID oxaprozin which exhibits weak sEH-phosphatase inhibitory activity [1]. SWE101 is a tool compound that was designed to aid investigations of the physiological and pathophysiological role of sEH phosphatase activity in vivo.
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 3
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 63.33
Molecular weight 375.04
XLogP 5.28
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
Canonical SMILES OC(=O)CCCc1oc(c(n1)c1ccc(c(c1)Cl)Cl)c1ccccc1
Isomeric SMILES OC(=O)CCCc1oc(c(n1)c1ccc(c(c1)Cl)Cl)c1ccccc1
InChI InChI=1S/C19H15Cl2NO3/c20-14-10-9-13(11-15(14)21)18-19(12-5-2-1-3-6-12)25-16(22-18)7-4-8-17(23)24/h1-3,5-6,9-11H,4,7-8H2,(H,23,24)
InChI Key UIADWSXPNFQQCZ-UHFFFAOYSA-N
Bioactivity Comments
SWE101 inhibits the phosphatase activity of human and rat sEH, but neither the hydrolase or phosphatase activities of mouse sEH are inhibited [2]. It also exhibits low potency COX enzyme inhibitory activity. At a concentration of 10 μM SWE101 is inactive at PPARs (α, β/δ), FXR, LXRα and LXRβ. SWE101 inhibits the phosphatase activity of the full-length human enzyme with IC50 of 9 μM. This is a reduced potency compared to the IC50 determined for inhibition of the isolated phosphatase domain-containing N-terminal.
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
epoxide hydrolase 2 Hs Inhibitor Inhibition 6.5 pKd - 2
pKd 6.5 (Kd 3x10-7 M) [2]
Description: Binding affinity for the N-terminal domain of sEH by isothermal titration calorimetry.
epoxide hydrolase 2 Hs Inhibitor Inhibition 7.2 pIC50 - 2
pIC50 7.2 (IC50 5.8x10-8 M) [2]
Description: Inhibition of sEH's phosphatase activity.
COX-2 Hs Inhibitor Inhibition 6.4 pIC50 - 2
pIC50 6.4 (IC50 4.2x10-7 M) [2]
COX-1 Hs Inhibitor Inhibition 5.9 pIC50 - 2
pIC50 5.9 (IC50 1.2x10-6 M) [2]