NVR 3-778 is a first-in-class, potent and oral bioavailable capsid assembly modulator against the hepatitis B virus [HBV CAM]. It belongs to the SBA (sulfamoylbenzamide) class, with anti-HBV activity.
Physicochemical Properties
| Molecular Formula | C18H16F4N2O4S |
| Molecular Weight | 432.38925743103 |
| Exact Mass | 432.076 |
| Elemental Analysis | C, 50.00; H, 3.73; F, 17.58; N, 6.48; O, 14.80; S, 7.41 |
| CAS # | 1445790-55-5 |
| Related CAS # | 2093094-04-1 (hydrate);1445790-55-5 (free); |
| PubChem CID | 89663273 |
| Appearance | White to off-white solid powder |
| Density | 1.6±0.1 g/cm3 |
| Index of Refraction | 1.606 |
| LogP | 3.13 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 9 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 29 |
| Complexity | 672 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | S(C1C(=CC=C(C(NC2C=C(C(=C(C=2)F)F)F)=O)C=1)F)(N1CCC(CC1)O)(=O)=O |
| InChi Key | KKMFSVNFPUPGCA-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C18H16F4N2O4S/c19-13-2-1-10(18(26)23-11-8-14(20)17(22)15(21)9-11)7-16(13)29(27,28)24-5-3-12(25)4-6-24/h1-2,7-9,12,25H,3-6H2,(H,23,26) |
| Chemical Name | 4-Fluoro-3-((4-hydroxypiperidin-1-yl)sulfonyl)-N-(3,4,5-trifluorophenyl)benzamide |
| Synonyms | NVR 3 778; NVR3 778; NVR-3-778; K-89; K 89; K89; NVR3778; NVR 3778; NVR-3778 |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| ln Vitro | Viral replication is inhibited by NVR 3-778, which targets the HBV core protein [1]. NVR 3-778 has an average antiviral effect EC50 of 0.40 µM in HepG2.2.15 cells, which means that it can prevent the generation of viral particles containing infectious HBV DNA [1]. Nucleos(t)ide inhibitors of HBV replication do not cause cross-resistance when used with NVR 3-778, which demonstrates genotype-wide antiviral efficacy [1]. NVR 3-778 prevents the generation of particles containing HBV DNA and HBV RNA, viral replication, and pregenomic RNA encapsidation [1]. With an EC50 of 0.81 µM against HBV DNA and 3.7 to 4.8 µM against HBV antigen and intracellular HBV RNA, NVR 3-778 also prevents de novo infection and viral replication in primary human hepatocytes [1]. When 10%, 20%, and 40% human serum were present, the EC50 values of NVR 3-778 rose by 4.5, 9.3, and 15.8 times, respectively [1]. |
| ln Vivo | Following oral delivery to dogs, NVR 3-778 (1.5 mg/kg; ig) demonstrated mean Cmax and AUC0–inf values of 0.56 µg/ml and 3.50 µg·h/ml, respectively. It was found that the average oral bioavailability was 84.6% [1]. |
| Animal Protocol |
Animal/Disease Models: Dog [1] Doses: 1.5 mg/kg (pharmacokinetic/PK/PK analysis) Route of Administration: po (oral gavage) Experimental Results: Mean Cmax and AUC0–inf values were 0.56 µg/ml and 3.50 µg·h/ml, oral Bioavailability is 84.6%. |
| References |
[1]. Preclinical Characterization of NVR 3-778, a First-in-Class Capsid Assembly Modulator against Hepatitis B Virus. Antimicrob Agents Chemother. 2018 Dec 21;63(1). |
Solubility Data
| Solubility (In Vitro) |
DMSO : 98 ~250 mg/mL (226.64 ~578.18 mM) Ethanol : ~98 mg/mL |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.81 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 (4.81 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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. Solubility in Formulation 3: ≥ 2.08 mg/mL (4.81 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly.. Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.08 mg/mL (4.81 mM) (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3127 mL | 11.5636 mL | 23.1273 mL | |
| 5 mM | 0.4625 mL | 2.3127 mL | 4.6255 mL | |
| 10 mM | 0.2313 mL | 1.1564 mL | 2.3127 mL |