GS-0938 (PSI352938; PSI938) is a novel and potent HCV NS5B inhibitor with the potential to be used for the treatment of HCV infection.
Physicochemical Properties
| Molecular Formula | C16H23FN5O6P |
| Molecular Weight | 431.3612 |
| Exact Mass | 431.137 |
| CAS # | 1231747-17-3 |
| PubChem CID | 46863668 |
| Appearance | Typically exists as solid at room temperature |
| LogP | 2.311 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 11 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 29 |
| Complexity | 663 |
| Defined Atom Stereocenter Count | 4 |
| SMILES | O=P1(OC(C)C)OC[C@]2([H])[C@@]([C@@](C)(F)[C@H](N3C(N=C(N)N=C4OCC)=C4N=C3)O2)([H])O1 |
| InChi Key | PVRFQJIRERYGTQ-UYISCHNFSA-N |
| InChi Code | InChI=1S/C16H23FN5O6P/c1-5-24-13-10-12(20-15(18)21-13)22(7-19-10)14-16(4,17)11-9(26-14)6-25-29(23,28-11)27-8(2)3/h7-9,11,14H,5-6H2,1-4H3,(H2,18,20,21)/t9-,11-,14-,16-,29?/m1/s1 |
| Chemical Name | 9-[(4aR,6R,7R,7aR)-7-fluoro-7-methyl-2-oxo-2-propan-2-yloxy-4,4a,6,7a-tetrahydrofuro[3,2-d][1,3,2]dioxaphosphinin-6-yl]-6-ethoxypurin-2-amine |
| Synonyms | GS-0938 PSI352938 PSI938 GS0938 PSI-352938 PSI-938 GS 0938 |
| 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 | At 50% effective doses (EC50) of 0.13±0.076 μM and 3.0±1.4 nM, respectively, PSI-352938 (PSI-938) and PSI-353661 suppress HCV genotype (GT) 1b replicon replication. They are also effective against GT 1a, with similar action. Viral infections and 2a replicons. The identical 5'-triphosphate metabolite, PSI-352666, is produced by the metabolism of PSI-352938 and PSI-353661. This metabolite exhibits comparable action against NS5B polymerase of GT 1–4 [1]. PSI-352938 (PSI-938) is a new cyclic phosphate prodrug of β-D-2'-deoxy-2'-α-fluoro-2'-β-C-methylguanosine 5'-monophosphate, Has significant anti-HCV activity. Similar action is shown by PSI-352938 (PSI-938), which ranges in EC50 values from 0.13 to 0.20 μM and in EC90 values from 0.35 to 0.74 μM against genotype 1a, 1b, and 2a replicons. PSI-352938 (PSI-938) also effectively inhibits HCV replication in infectious virus detection: EC50 and EC90 values against H77 infectious virus are 0.28±0.083 μM and 0.63±0.018 μM, respectively, and EC50 against H77 infectious virus and EC90 values were 0.39±0.31 μM and 1.16±0.64 μM, respectively, against JFH-1 infectious virus. In contrast, PSI-352938 was not active against HBV or HIV at the highest concentration tested (EC50>100 μM) [2]. |
| References |
[1]. Lam AM, et al. Hepatitis C virus nucleotide inhibitors PSI-352938 and PSI-353661 exhibit a novel mechanism of resistance requiring multiple mutations within replicon RNA. J Virol. 2011 Dec;85(23):12334-42. [2]. Lam AM, et al. Inhibition of hepatitis C virus replicon RNA synthesis by PSI-352938, a cyclic phosphate prodrug of β-D-2'-deoxy-2'-α-fluoro-2'-β-C-methylguanosine. Antimicrob Agents Chemother. 2011 Jun;55(6):2566-75 |
| Additional Infomation | See also: Psi-352938 (annotation moved to). |
Solubility Data
| 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 |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3182 mL | 11.5912 mL | 23.1825 mL | |
| 5 mM | 0.4636 mL | 2.3182 mL | 4.6365 mL | |
| 10 mM | 0.2318 mL | 1.1591 mL | 2.3182 mL |