FXR DUBTAC modulator-1
FXR DUBTAC modulator-1 is a deubiquitinase-targeting chimeric molecule (DUBTAC) that targets FXR, with a Ka value of 2.12e-5 M for FXR. FXR DUBTAC modulator-1 recruits the deubiquitinase OTUB1, binds to OTUB1 and forms a ternary complex with FXR, reduces the polyubiquitination level of FXR, prevents FXR degradation via the ubiquitin-proteasome pathway, and elevates the protein level of FXR. FXR DUBTAC modulator-1 can be used in the research of cholestatic liver injury.
For research use only. We do not sell to patients.
- CAS No.: 3081876-96-9
- Formula: C43H66N4O7
- Molecular Weight:751.01
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
FXR DUBTAC modulator-1 (compound D11) (1-10 μM; 24 h) significantly increases FXR protein expression in HepG2 cells while maintaining 70.71% cell viability at 50 μM[1].
FXR DUBTAC modulator-1 (0.1-10 μM) increases FXR protein levels in a dose-dependent manner in HepG2 cells[1].
FXR DUBTAC modulator-1 (1 μM; 1-8 h) increases FXR protein levels in a time-dependent manner in HepG2 cells, with detectable increases starting at 1 h and continuing through 8 h[1].
FXR DUBTAC modulator-1 stabilizes FXR protein by promoting its deubiquitination in HepG2 cells, as evidenced by reduced FXR polyubiquitination and increased FXR protein levels following treatment[1].
FXR DUBTAC modulator-1 binds to purified FXR protein with a dissociation constant (Kd) of 2.12 × 10-5 M, as measured by surface plasmon resonance[1].
FXR DUBTAC modulator-1's FXR protein-stabilizing effect is dependent on OTUB1 in HepG2 cells, as knockdown of OTUB1 eliminates FXR DUBTAC modulator-1-induced FXR stabilization[1].
FXR DUBTAC modulator-1 (2 μM; up to 120 min) demonstrates favorable metabolic stability in mouse and rat liver microsomes, with a half-life exceeding 120 min for both species[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:1 μM, 10 μM, 50 μM
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Incubation Time:24 h (1 μM, 10 μM); no time specified (50 μM)
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Result:Significantly increased FXR protein expression at 1 μM and further increased expression at 10 μM.
Maintained 70.71% cell viability at 50 μM.
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Cell Line:HepG2 cells
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Concentration:1 μM
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Incubation Time:1 h, 2 h, 4 h, 8 h
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Result:Induced stabilization of FXR protein in a time-dependent manner, with FXR protein levels beginning to increase at 1 h after incubation.
FXR DUBTAC modulator-1 (1-2.5 mg/kg; i.p.; daily; 3 days) alleviates cholestatic liver injury in an OTUB1-dependent manner, as its hepatoprotective effects are completely abrogated by OTUB1 knockdown[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J (male, 6 weeks old, 20 g, ANIT-induced cholestasis)[1]
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Dosage:1 mg/kg; 2.5 mg/kg
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Administration:i.p.; daily; 5 days
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Result:Significantly increased hepatic FXR protein levels in ANIT-induced cholestatic mice.
Caused significant, dose-dependent reductions in serum ALT, AST, ALP, and TBA levels.
Showed efficacy comparable to obeticholic acid (OCA) at 2.5 mg/kg at 1 mg/kg, and superior efficacy over OCA in reducing transaminases.
Improved liver histology as shown by hematoxylin-eosin (H&E) staining.
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Animal Model:C57BL/6J (male, 6 weeks old, OTUB1 knockdown via AAV8-shRNA, ANIT-induced cholestasis)[1]
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Dosage:1 mg/kg; 2.5 mg/kg
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Administration:i.p.; daily; 3 days
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Result:Reversed ANIT-induced downregulation of hepatic FXR protein, significantly reduced elevated serum ALT, AST, ALP, and TBA levels, and improved liver histology in control shRNA-injected mice.
Failed to restore hepatic FXR protein levels, reduce serum cholestasis markers, or improve liver histology in OTUB1-knockdown mice.
Chemical Information
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CAS No. 3081876-96-9
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Molecular Weight 751.01
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Formula C43H66N4O7
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SMILES
O[C@@H]1CC[C@@]2([C@]3(CC[C@@]4([C@@](CC[C@]4([C@@]3([C@@H](C([C@]2([H])C1)CC)O)[H])[H])([H])[C@@H](CCC(NCCCNC(CCC5=CC=C(N6C(CN(CC6)C(C=C)=O)=O)O5)=O)=O)C)C)[H])C
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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)
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