PROTAC sEH degrader-5
PROTAC sEH degrader-5 is a highly efficient PROTAC degrader that targets and degrades soluble epoxide hydrolase (sEH) by recruiting cereblon. PROTAC sEH degrader-5 directly inhibits the hydrolase activity of human and mouse sEH, with pIC50 values of 10.36 and 8.41, respectively. PROTAC sEH degrader-5 alleviates LPS (HY-D1056)-induced acute inflammation in vivo. PROTAC sEH degrader-5 can be used in studies related to LPS-induced acute inflammation.
(Pink: Epoxide Hydrolase ligand (HY-113974); Blue: Cereblon ligand (HY-103596); Black: linker).
For research use only. We do not sell to patients.
- CAS No.: 3123230-60-1
- Formula: C53H70N8O10
- Molecular Weight:979.17
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Biological Activity
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HepG2 | DC50 |
2.9 nM
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Degradation of sEH protein in human HepG2 cells assessed via immunoblot after 6 hrs of treatment.
Degradation of sEH protein in human HepG2 cells assessed via immunoblot after 6 hrs of treatment.
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42469598 |
PROTAC sEH degrader-5 (compound 1d) (0.1-1000 nM; 6-24 h) potently degrades sEH in HepG2 cells via the proteasome pathway, with a DC50 of 2.9 nM, and its activity depends on intact CRBN binding[1].
PROTAC sEH degrader-5 potently inhibits the hydrolase activity of recombinantly purified human sEH (pIC50 = 10.36) and mouse sEH (pIC50 = 8.41)[1].
PROTAC sEH degrader-5 (1 μM; 24 h) induces 61.3 ± 4.7% degradation of sEH in HepG2 cells[1].
sEH degradation induced by PROTAC sEH degrader-5 (100 nM; 24 h) is significantly attenuated by MG132 (HY-13259) (5 μM), whereas Chloroquine (HY-17589A) (5 μM) exerts no obvious effect, indicating that sEH degradation is mediated via the proteasome pathway[1].
The methylated derivative of PROTAC sEH degrader-5 (100 nM; 6 h) with a modified CRBN-binding moiety fails to effectively reduce sEH protein levels, indicating that an intact CRBN-binding moiety is essential for its sEH-degrading activity[1].
PROTAC sEH degrader-5 (100 nM; 6 h) significantly degrades sEH in the cytoplasmic fraction of HepG2 cells, while the level of sEH in the peroxisomal fraction shows no obvious change[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HepG2 cells
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Concentration:0.1-1000 nM (6 h); 1 μM (24 h); 100 nM (6 h, 24 h with 5 μM MG132 or 5 μM Chloroquine)
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Incubation Time:6 h; 24 h
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Result:Achieved 61.3% degradation of sEH at 1 μM for 24 h.
Significantly reduced sEH protein levels at 100 nM for 6 h.
Showed maximal sEH degradation of 73% with a DC50 value of 2.9 nM in concentration-dependent testing over 6 h.
Attenuated sEH degradation when co-treated with 5 μM MG132, but no impact when co-treated with 5 μM chloroquine.
Methylated derivative with disrupted CRBN binding had no effect on sEH abundance.
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Cell Line:HepG2 cells
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Concentration:1 μM
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Incubation Time:24 h; 48 h; 72 h
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Result:Showed no evident cytotoxicity.
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Cell Line:HepG2 cells
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Concentration:1 μM
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Incubation Time:24 h
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Result:Showed no significant difference in relative EPHX2 mRNA expression compared to control or DMSO-treated groups.
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Cell Line:HepG2 cells (cytosolic S10 and peroxisomal P10 fractions)
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Concentration:100 nM
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Incubation Time:6 h
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Result:Reduced sEH protein levels in cytosolic (S10) fraction compared to control groups.
Reduced sEH protein levels in peroxisomal (P10) fraction compared to control groups.
PROTAC sEH degrader-5 (10 mg/kg; i.p.) reduces LPS-induced inflammatory cell infiltration and focal necrosis in the liver[1].
PROTAC sEH degrader-5 (10 mg/kg; i.p.) increases plasma levels of sEH upstream epoxy lipid substrates 9 (10)-EpOME, 12 (13)-EpOME, 11 (12)-EET, 14 (15)-EET and 8 (9)-EET, and elevates the ratios of EpOMEs/DiHOMEs and EETs/DiHETs[1].
PROTAC sEH degrader-5 (10 mg/kg; i.p.) significantly attenuates the LPS-induced upregulation of Il-6, Mcp-1 and Il-10 mRNA expression in the liver[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:LPS-induced acute inflammation[1]
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Dosage:10 mg/kg
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Administration:i.p.; 12 h before LPS; samples collected 6 h after LPS
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Result:Reduced hepatic sEH protein levels.
Attenuated LPS-induced Il-6, Mcp-1, and Il-10 mRNA elevation.
Attenuated hepatic inflammatory cell infiltration and focal necrosis.
Increased plasma epoxy lipid substrates and EpOMEs/DiHOMEs and EETs/DiHETs ratios.
Chemical Information
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CAS No. 3123230-60-1
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Molecular Weight 979.17
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Formula C53H70N8O10
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SMILES
O=C(NC12C[C@H](C[C@H](C2)C3)C[C@H]3C1)N[C@H]4CC[C@@H](CC4)OC5=CC=C(C=C5)C(N6CCN(CC6)CC(NCCCCCCCCNC(COC7=CC=CC(C(N8C9C(NC(CC9)=O)=O)=O)=C7C8=O)=O)=O)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PROTAC sEH degrader-5 Related Classifications
HY-187425 Related Classifications
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- PROTAC sEH degrader-5
- 3123230-60-1
- PROTAC sEH degrader5
- PROTAC sEH degrader 5
- PROTACs
- Epoxide Hydrolase
- recombinant purified human sEH
- mouse sEH
- HepG2 cells
- cytosolic fractions
- proteasome pathway
- peroxisomal fractions
- EPHX2 gene
- LPS-induced acute inflammation
- E3 ubiquitin ligase CRBN
- soluble epoxide hydrolase
- Inhibitor
- inhibitor
- inhibit