| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Vonafexor (formerly EYP001) targets the farnesoid X receptor (FXR), acting as a selective FXR agonist with an EC50 of 41 nM for human FXR activation [3]
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| ln Vitro |
When paired with entecavir or tenofovir, vonafexor (EYP001) has additive effects that significantly reduce HBV DNA, HBsAg, and HBeAg secretion in HepaRG cells by inhibiting the HBV replication cycle [3].
In HBV-infected HepaRG cells, Vonafexor (1 μM) significantly reduced HBV DNA levels by ~40% and HBsAg levels by ~30% compared to the control group [3] - The compound exhibited additive anti-HBV effects when combined with nucleoside analogues (e.g., entecavir) in HepaRG cells: co-treatment with Vonafexor (1 μM) and entecavir (100 nM) reduced HBV DNA by ~75%, which was significantly higher than either agent alone [3] - Vonafexor (0.1-10 μM) dose-dependently activated FXR-mediated gene expression (e.g., BSEP, SHP) in HepaRG cells, confirming FXR agonistic activity [3] |
| ln Vivo |
In a phase I clinical study in healthy subjects, oral administration of Vonafexor (single doses of 10-300 mg or multiple doses of 30-100 mg once daily for 14 days) resulted in dose-dependent activation of FXR biomarkers (e.g., increased serum FGF19 levels, decreased serum bile acid concentrations) [3]
- In a phase II clinical study in chronic hepatitis B (CHB) patients, Vonafexor (100 mg once daily for 12 weeks) combined with entecavir reduced HBV DNA by an additional ~0.8 log10 IU/mL compared to entecavir monotherapy, and 25% of patients achieved HBsAg reduction ≥0.5 log10 IU/mL [2] - The compound did not cause significant elevation of liver function markers (ALT, AST) in CHB patients, indicating liver safety in the treatment setting [1] |
| Enzyme Assay |
FXR activation assay was performed using a luciferase reporter gene system. HepG2 cells were transfected with human FXR expression plasmid and FXR-responsive luciferase reporter plasmid. After incubation with serial dilutions of Vonafexor for 24 hours, luciferase activity was measured. EC50 values were calculated by fitting the dose-response curves of luciferase activity enhancement [3]
- FXR binding assay was conducted using a homogeneous time-resolved fluorescence (HTRF) method. Recombinant human FXR ligand-binding domain was incubated with fluorescently labeled FXR ligand and serial dilutions of Vonafexor. HTRF signals were measured to evaluate competitive binding, and binding affinity (Ki) was derived [3] |
| Cell Assay |
HBV inhibition assay in HepaRG cells: HepaRG cells were infected with HBV for 14 days to establish a chronic infection model. Cells were treated with Vonafexor (0.1-10 μM) alone or in combination with entecavir for 72 hours. HBV DNA levels were quantified by qPCR, and HBsAg levels were measured by ELISA [3]
- FXR target gene expression assay: HepaRG cells were treated with Vonafexor (0.1-10 μM) for 24 hours. Total RNA was extracted, and mRNA levels of FXR target genes (BSEP, SHP) were quantified by RT-qPCR [3] |
| ADME/Pharmacokinetics |
In healthy subjects, after oral administration of Vonafexor (100 mg once daily), the peak plasma concentration (Cmax) was 1.8 μg/mL, the area under the plasma concentration-time curve (AUC0-24h) was 22.3 μg·h/mL, and the terminal half-life (t1/2) was 18.5 hours [3]. - The oral bioavailability of this compound in humans is approximately 55%, and food intake can increase Cmax by approximately 30%, but has no significant effect on AUC [3]. - Vonafexor has a protein binding rate of 97% in human plasma [3]. - Vonafexor is mainly metabolized by cytochrome P450 3A4 (CYP3A4), and renal excretion is minimal (<5% of the total dose) [3].
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| Toxicity/Toxicokinetics |
In a Phase I clinical trial, Vonafexor was well tolerated in healthy subjects at doses up to 300 mg (single dose) and 100 mg (multiple doses over 14 days). The most common adverse events were mild gastrointestinal symptoms (nausea, diarrhea) and headache [3]. No significant changes in liver function (ALT, AST), kidney function (creatinine, blood urea nitrogen), or hematological parameters were observed in patients with chronic hepatitis B (CHB) treated with Vonafexor (100 mg once daily for 12 weeks) [1]. Vonafexor does not inhibit major cytochrome P450 isoenzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4) at therapeutic concentrations, suggesting a low risk of drug interactions [3].
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| References |
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| Additional Infomation |
Vonafexor (formerly known as EYP001) is a selective, orally active FXR agonist for the treatment of chronic hepatitis B (CHB) and non-alcoholic steatohepatitis (NASH) [3][4] - Its anti-HBV mechanism involves FXR-mediated inhibition of HBV transcription and replication, and synergistic effects with nucleoside/nucleotide analogs (NNAs) to enhance viral suppression [2][3] - The compound is currently in Phase II clinical development for CHB, and preliminary data show good safety and efficacy, including a reduction in HBsAg levels in some patients [2] - For NASH, Vonafexor is being evaluated for its ability to improve hepatic steatosis, inflammation, and fibrosis by regulating bile acid metabolism and lipid homeostasis through FXR activation [4]
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| Molecular Formula |
C19H15CL3N2O5SEXACTMASS
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|---|---|
| Molecular Weight |
489.7568
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| Exact Mass |
487.976
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| CAS # |
1192171-69-9
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| Related CAS # |
1192171-69-9;
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| PubChem CID |
67202717
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.604±0.06 g/cm3(Predicted)
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| Boiling Point |
680.5±65.0 °C(Predicted)
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| LogP |
4.8
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
30
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| Complexity |
733
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
XLGQSYUNOIJBNR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H15Cl3N2O5S/c20-12-2-1-3-13(21)18(12)30(27,28)24-8-6-23(7-9-24)14-4-5-15-11(17(14)22)10-16(29-15)19(25)26/h1-5,10H,6-9H2,(H,25,26)
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| Chemical Name |
4-chloro-5-[4-(2,6-dichlorobenzene-1- sulfonyl)piperazin-1-yl]-1-benzofuran-2-carboxylic acid
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| Synonyms |
VonafexorEyp001
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~83.33 mg/mL (~170.14 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.25 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.25 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.25 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0418 mL | 10.2091 mL | 20.4182 mL | |
| 5 mM | 0.4084 mL | 2.0418 mL | 4.0836 mL | |
| 10 mM | 0.2042 mL | 1.0209 mL | 2.0418 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT06425055 | RECRUITING | Drug: Vonafexor | Alport Syndrome | Enyo Pharma | 2024-07-05 | Phase 2 |
| NCT03812029 | COMPLETED | Drug: Vonafexor Other: Placebo |
Non-alcoholic Steatohepatitis | Enyo Pharma | 2019-01-30 | Phase 2 |
| NCT04465916 | TERMINATED | Drug: EYP001a Drug: Placebo |
Hepatitis B, Chronic | Enyo Pharma | 2020-05-12 | Phase 2 |
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