| Name | PSI-6206 |
| Description | PSI-6206 (RO 2433) (RO2433) is a selective HCV RNA polymerase inhibitor. |
| Kinase Assay | Protein Kinase Assays: The in vitro kinase assays are performed in 96-well plates (30 μL) at ambient temperature for 15–45 min using the recombinant glutathione S-transferase-fused kinase domains (4-100 ng, depending on specific activity). [γ33P]ATP is used as phosphate donor and polyGluTyr-(4:1) peptide as acceptor. With the exception of protein kinase C-α, cyclin-dependent kinase 1/cycB and protein kinase A are protamine sulfate (200 μg/mL), histone H1 (100 μg/mL), and the heptapeptide Leu-Arg-Arg-Ala-Ser-Leu-Gly (known as Kemptide Bachem) respectively and are used as peptide substrates. Assays are optimized for each kinase using the following ATP concentrations: 1.0 μM (c-Kit, c-Met, c-Fms, c-Raf-1, and RET), 2.0 μM (EGFR, erbB2, ErbB3, and ErbB4), 5.0 μM (c-abl), 8.0 μM (Flt-1, Flt-3, Flt-4, Flk, KDR, FGFR-1, and Tek), 10.0 μM (PDGFR-β, protein kinase C-α, and cyclin-dependent kinase 1), and 20.0 μM (c-Src and protein kinase A). The reaction is terminated by the addition of 20 μL 125 mM EDTA. Thirty μL (c-abl, c-Src, insulin-like growth factor-1R, RET-Men2A, and RET-Men2B) or 40 μL (all other kinases) of the reaction mixture is transferred onto Immobilon-polyvinylidene difluoride membrane, presoaked with 0.5% H3PO4 and mounted on a vacuum manifold. Vacuum is then applied and each well rinsed with 200 μL 0.5% H3PO4. Membranes are removed and washed four times with 1.0% H3PO4 and once with ethanol. Dried membranes are counted after mounting in a Packard TopCount 96-well frame and with the addition of 10 μL/well of Microscint. IC50 values (±SE) are calculated by linear regression analysis of the percentage inhibition and are averages of at least three determinations. |
| In vitro | PSI-6206 (RO2433), a deaminated derivative of PSI-6130, a potent and selective inhibitor of HCV NS5B polymerase, has been evaluated for its anti-HCV efficacy employing both a cell-based quantitative real-time RT-PCR assay and surrogate bovine viral diarrhea virus (BVDV) assays. It showed no activity or cytotoxicity in these assays. The formation of 5′-triphosphate (TP) forms of PSI-6130 (PSI-6130-TP) and RO2433 (RO2433-TP) progressively increased, achieving steady state levels after 48 hours. Notably, RO2433-TP effectively inhibits RNA synthesis by both the native HCV replicase from HCV replicon cells and the recombinant HCV polymerase NS5B, highlighting its potential mechanism of action against HCV replication. |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature. |
| Solubility Information | 10% DMSO+40% PEG300+5% Tween 80+45% Saline : 2 mg/mL (7.69 mM), Sonication is recommended.
DMSO : 60 mg/mL (230.57 mM), Sonication is recommended.
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| Keywords | RO-2433 | RO2433 | PSI-6206 | PSI6206 | PSI 6206 | Inhibitor | inhibit | Hepatitis C virus | HCVProtease | HCV replicon | HCV Protease | HCV | GS331007 | GS 331007 |
| Inhibitors Related | EIDD-1931 | AG-1478 | Methyl 2-amino-5-bromobenzoate | RO8191 | Ribavirin | Sofosbuvir | Deferiprone | Ombitasvir | Artemisinin | HCV-IN-29 | Honokiol | Resiquimod |
| Related Compound Libraries | Featured Fragment Library | Bioactive Compound Library | Anti-Viral Compound Library | Inhibitor Library | NO PAINS Compound Library | Immunology/Inflammation Compound Library | Bioactive Compounds Library Max | Fluorochemical Library | Covalent Inhibitor Library | Anti-Infection Compound Library | High Solubility Pharmacophore Fragment Library | Nucleotide Compound Library |
United States
