2. PROTAC Cell Cycle/DNA Damage
  3. DUBTACs Deubiquitinase
  4. 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.

FXR DUBTAC modulator-1

FXR DUBTAC modulator-1 Chemical Structure

CAS No. : 3081876-96-9

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FXR DUBTAC modulator-1 Related Antibodies

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Description

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[1].

In Vitro

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.

FXR DUBTAC modulator-1 Related Antibodies

Western Blot Analysis[1]

Cell Line: HepG2 cells
Concentration: 1 μM, 10 μM, 50 μM
Incubation Time: 24 h (1 μM, 10 μM); no time specified (50 μM)
Result: Significantly increased FXR protein expression at 1 μM and further increased expression at 10 μM.
Maintained 70.71% cell viability at 50 μM.

Western Blot Analysis[1]

Cell Line: HepG2 cells
Concentration: 1 μM
Incubation Time: 1 h, 2 h, 4 h, 8 h
Result: Induced stabilization of FXR protein in a time-dependent manner, with FXR protein levels beginning to increase at 1 h after incubation.
Parmacokinetics
Species Dose Route T1/2 Tmax Cmax AUC0-t CL
Rat[1] 2.5 mg/kg i.p. 11.00 h 1.50 h 18.84 ng/mL 82.53 ng·h/mL 419.78 mL/min/kg
Rat[1] 5 mg/kg i.p. 4.00 h 2.00 h 28.77 ng/mL 206.21 ng·h/mL 6.45 mL/min/kg
In Vivo

FXR DUBTAC modulator-1 (compound D11) (1-2.5 mg/kg; i.p.; daily; 5 days) stabilizes hepatic FXR protein and exerts potent, dose-dependent hepatoprotective effects against ANIT-induced cholestasis, with efficacy comparable to or better than OCA at equivalent or lower doses[1].
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.

Animal Model: C57BL/6J (male, 6 weeks old, 20 g, ANIT-induced cholestasis)[1]
Dosage: 1 mg/kg; 2.5 mg/kg
Administration: i.p.; daily; 5 days
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.
Animal Model: C57BL/6J (male, 6 weeks old, OTUB1 knockdown via AAV8-shRNA, ANIT-induced cholestasis)[1]
Dosage: 1 mg/kg; 2.5 mg/kg
Administration: i.p.; daily; 3 days
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.
Molecular Weight

751.01

Formula

C43H66N4O7
CAS No.
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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Purity & Documentation
References
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FXR DUBTAC modulator-1 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

FXR DUBTAC modulator-13081876-96-9FXR DUBTAC modulator1FXR DUBTAC modulator 1DUBTACsDeubiquitinaseDeubiquitinase-targeting chimerasDUBsdeubiquitinaseubiquitin-proteasome systemfarnesoid X receptorα-naphthylisothiocyanate-induced cholestasisrat liver microsomesOTUB1HepG2 cellscholestatic liver injurypolyubiquitinationmiceInhibitorinhibitorinhibit

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