PSI-6206 (also known as GS331007 and RO-2433), a deaminated derivative of PSI-6130, is a novel, potent and selective HCV NS5B polymerase inhibitor. In a subgenomic HCV replicon assay system, PSI-6206 and 2'-C-methylcytidine were shown to be strong and specific inhibitors of HCV replication. Comparing PSI-6206 to 2'-C-methylcytidine in the HCV replicon assay, it demonstrates lower cellular toxicity and more inhibitory activity.
Physicochemical Properties
| Molecular Formula | C10H13FN2O5 |
| Molecular Weight | 260.2190 |
| Exact Mass | 260.08 |
| Elemental Analysis | C, 46.16; H, 5.04; F, 7.30; N, 10.77; O, 30.74 |
| CAS # | 863329-66-2 |
| Related CAS # | PSI-6206-13C,d3;1256490-42-2 |
| PubChem CID | 11311503 |
| Appearance | White to off-white solid powder |
| Density | 1.6±0.1 g/cm3 |
| Melting Point | 237-238℃ |
| Index of Refraction | 1.596 |
| LogP | -0.77 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 2 |
| Heavy Atom Count | 18 |
| Complexity | 415 |
| Defined Atom Stereocenter Count | 4 |
| SMILES | C[C@]1([C@H](O)[C@@H](CO)O[C@H]1N1C=CC(=O)NC1=O)F |
| InChi Key | ARKKGZQTGXJVKW-VPCXQMTMSA-N |
| InChi Code | InChI=1S/C10H13FN2O5/c1-10(11)7(16)5(4-14)18-8(10)13-3-2-6(15)12-9(13)17/h2-3,5,7-8,14,16H,4H2,1H3,(H,12,15,17)/t5-,7-,8-,10-/m1/s1 |
| Chemical Name | 1-[(2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]pyrimidine-2,4-dione |
| Synonyms | RO-2433; RO2433; RO 2433; PSI6206; PSI 6206; PSI-6206; GS-331007; GS 331007; GS331007 |
| 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
| Targets | HCV (EC90 >100 μM) |
| ln Vitro | PSI-6206 (RO 2433) is subjected to surrogate bovine viral diarrhea virus (BVDV) assays as well as a cell-based quantitative real-time RT-PCR assay to assess its anti-HCV activity. No assay shows any activity or cytotoxicity from PSI-6206[1]. PSI-6130 (PSI-6130-TP) and RO2433 (RO2433-TP) both form 5′-triphosphate (TP) that steadily increases over time, reaching steady state levels after 48 hours. Additionally, RO2433-TP prevents both the recombinant HCV polymerase NS5B and the native HCV replicase that is separated from HCV replicon cells from synthesizing RNA[2]. A strong and specific inhibitor of HCV NS5B polymerase, PSI-6206 (RO2433) is the deaminated derivative of PSI-6130[3]. |
| References |
[1]. Design, Synthesis, and Antiviral Activity of 2'-Deoxy-2'-fluoro-2'-C-methyl-cytidine, a Potent Inhibitor of Hepatitis C Virus Replication. J Med Chem. 2005 Aug 25;48(17):5504-8. [2]. Characterization of the metabolic activation of hepatitis C virus nucleoside inhibitor beta-D-2'-Deoxy-2'-fluoro-2'-C-methylcytidine (PSI-6130) and identification of a novel active 5'-triphosphate species. J Biol Chem. 2007 Oct 12;282(41):29. [3]. An efficient and diastereoselective synthesis of PSI-6130: a clinically efficacious inhibitor of HCV NS5B polymerase. J Org Chem. 2009 Sep 4;74(17):6819-24. |
Solubility Data
| Solubility (In Vitro) |
DMSO: ~52 mg/mL (~199.8 mM) Ethanol: ~24 mg/mL (~92.2 mM) Water: ~52 mg/mL (~199.8 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.61 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 25.0 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: ≥ 2.5 mg/mL (9.61 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 25.0 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: ≥ 2.5 mg/mL (9.61 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.8429 mL | 19.2145 mL | 38.4290 mL | |
| 5 mM | 0.7686 mL | 3.8429 mL | 7.6858 mL | |
| 10 mM | 0.3843 mL | 1.9215 mL | 3.8429 mL |