| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
VCH-916 targets the hepatitis C virus NS5B RNA-dependent RNA polymerase (RdRp), an essential enzyme for viral RNA replication . As a non-nucleoside allosteric inhibitor, it binds non-competitively to the NS5B polymerase at a site distinct from the active site, thereby inhibiting viral RNA synthesis . VCH-916 demonstrates equipotent activity against both HCV genotype 1a and 1b replicons and shows >100-fold selectivity for HCV NS5B over human DNA polymerases alpha, beta, and gamma (IC50 > 100 μM) .
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|---|---|
| ln Vitro |
VCH-916 demonstrates sub-micromolar inhibitory activity against HCV replicons of genotypes 1a and 1b, with equipotent activity against both subtypes . In replicon assays, the compound exhibits a therapeutic index (CC50/EC50) exceeding 400, indicating a favorable safety margin . The compound is highly selective for HCV NS5B polymerase, showing no significant inhibition of human DNA polymerases alpha, beta, and gamma at concentrations up to 100 μM . In human liver microsomes and hepatocytes, VCH-916 displays relatively stable metabolic profiles, with both oxidation and glucuronidation pathways involved in its biotransformation . No evidence of covalent binding to microsomal proteins upon oxidative bioactivation has been observed .
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| ln Vivo |
VCH-916 has been evaluated in a Phase Ib clinical trial (NCT00623649) in treatment-naive or experienced subjects with chronic HCV genotype 1 infection . The study employed a multiple ascending dose design with VCH-916 administered at doses of 100 mg three times daily, 200 mg three times daily, 300 mg twice daily, or 400 mg twice daily for three days . The primary objectives were to assess antiviral activity, safety, and tolerability, while secondary objectives included pharmacokinetic profiling and the relationship between plasma VCH-916 levels and HCV RNA reduction . Detailed viral load reduction data are not available in the published search results.
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| Enzyme Assay |
The non-cell-based enzyme inhibition assays for VCH-916 utilized recombinant HCV NS5B polymerase enzymes derived from genotypes 1a and 1b. Polymerase activity was measured by monitoring the incorporation of radiolabeled nucleotides into RNA templates. VCH-916 was tested across a range of concentrations, and IC50 values were calculated from concentration-response curves. The compound demonstrated sub-micromolar IC50 values against both genotype 1a and 1b polymerases . Selectivity studies evaluated VCH-916 against human DNA polymerases alpha, beta, and gamma, showing IC50 values > 100 μM, indicating >100-fold selectivity for HCV NS5B over host polymerases .
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| Cell Assay |
Cellular antiviral activity of VCH-916 was assessed using HCV subgenomic replicon systems for genotypes 1a and 1b. Cell lines (e.g., Huh-7 cells) harboring stable replicons were cultured in appropriate media and treated with serially diluted VCH-916 for a specified duration (typically 3 days). HCV RNA replication was quantified by measuring luciferase reporter activity or by real-time PCR. EC50 values (concentration required to reduce HCV RNA replication by 50%) were calculated from concentration-response curves. Cytotoxicity was assessed in parallel using standard cell viability assays (e.g., MTT or CellTiter-Glo) to determine CC50 values. The therapeutic index (CC50/EC50) for VCH-916 in replicon assays was reported as >400 .
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| Animal Protocol |
Preclinical pharmacokinetic studies of VCH-916 were conducted in rats and dogs following intravenous (iv) and oral (po) administration . In rats, the routes of excretion and liver distribution were determined following oral administration of 14C-labeled VCH-916. Recovery of radioactivity was nearly complete (80%) within 24 hours post-dosing, with the majority of the dose excreted in feces, indicating fecal elimination as the primary route . The exposure of VCH-916 in rat liver was 5-fold higher than in plasma, suggesting favorable distribution to the target organ . In both rats and dogs, VCH-916 displayed low total body clearance and excellent oral bioavailability (>40%) .
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| ADME/Pharmacokinetics |
VCH-916 exhibits excellent ADME properties with high oral bioavailability (>40%) in rats and dogs and low total body clearance . Plasma protein binding is extensive (>98%) across all species tested . Absorption potential is high, as demonstrated by high permeability in Caco-2 cells and lack of recognition by intestinal efflux proteins; VCH-916 shows no significant effect on digoxin permeability, indicating no Pgp inhibition . In human Phase I studies, under fasting conditions, AUC appeared dose-proportional between 50-200 mg but increased in a more-than-proportional manner between 200-600 mg; Cmax increased roughly proportionally across the entire dose range . Food did not affect the extent of absorption (AUC) but modestly decreased Cmax . No major circulating metabolites (accounting for ≥10% of parent AUC) were observed in human plasma . VCH-916 displays plasma exposure supporting twice-daily (BID) dosing at doses ≥200 mg . The compound is mainly eliminated in rat through feces, and exhibits relatively stable metabolic profiles in human microsomes and hepatocytes, with both oxidation (CYP2C8, 3A4) and glucuronidation (UGT1A3, 1A8, 2B7, 2B17) pathways involved in its biotransformation without evidence of reactive intermediate formation .
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| Toxicity/Toxicokinetics |
In a Phase I single ascending dose study in healthy volunteers, VCH-916 was safe and well tolerated at doses up to 600 mg . The most commonly reported adverse events were throat irritation and headache; additional events included blurred vision, nausea, decreased blood pressure, and somnolence . No serious adverse events or treatment discontinuations were reported, and 96% of all reported adverse events were mild to moderate . Three severe adverse events (dyspnea, headache, nausea) were experienced by a single subject in the 600 mg dose group, but the frequency of adverse events did not appear to be dose-related . No clinically significant changes in vital signs, laboratory results, or ECG measurements were observed . VCH-916 demonstrates limited potential to cause CYP inhibition, CYP induction, or Pgp inhibition, reducing the likelihood of drug-drug interactions . For laboratory research, the compound is classified as non-hazardous, but standard safety precautions should be followed when handling .
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| References |
| Molecular Formula |
C26H37NO4S
|
|---|---|
| Molecular Weight |
459.64
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| Exact Mass |
459.244
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| CAS # |
914778-92-0
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| Related CAS # |
1200133-34-1
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| PubChem CID |
11963194
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
6.1
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
32
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| Complexity |
694
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O(C)[C@@H]1CC[C@@H](N(C2=C(C(O)=O)SC(C3CCCCC=3)=C2)C(=O)[C@H]2CC[C@@H](CC2)C)CC1
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| InChi Key |
LNYKGELUODVSNS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H37NO4S/c1-17-8-10-19(11-9-17)25(28)27(20-12-14-21(31-2)15-13-20)22-16-23(32-24(22)26(29)30)18-6-4-3-5-7-18/h6,16-17,19-21H,3-5,7-15H2,1-2H3,(H,29,30)
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| Chemical Name |
5-(cyclohexen-1-yl)-3-[(4-methoxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylic acid
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| Synonyms |
VCH-916 Free acid; VCH-916 free acid(1200133-34-1 free base); VCH-916 (free base); orb1296187
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1756 mL | 10.8781 mL | 21.7562 mL | |
| 5 mM | 0.4351 mL | 2.1756 mL | 4.3512 mL | |
| 10 mM | 0.2176 mL | 1.0878 mL | 2.1756 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 |
| NCT00623649 | Completed | Drug: VCH 916 Drug: Placebo |
HCV Infection | Vertex Pharmaceuticals Incorporated | 2007-11 | Phase 1 |
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