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| 10mg |
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| 25mg |
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Purity: ≥98%
RO-9187 is a novel and potent inhibitor of HCV virus replication with IC50 of 171 nM. RO-0622 and RO-9187 were excellent substrates for deoxycytidine kinase and were phosphorylated with efficiencies up to 3-fold higher than deoxycytidine. As compared with previous reports on ribonucleosides, higher levels of triphosphate were formed from RO-9187 in primary human hepatocytes, and both compounds were potent inhibitors of HCV virus replication in the replicon system (IC(50) = 171 +/- 12 nM and 24 +/- 3 nM for RO-9187 and RO-0622, respectively; CC(50) >1 mM for both). Both compounds inhibited RNA synthesis by HCV polymerases from either HCV genotypes 1a and 1b or containing S96T or S282T point mutations with similar potencies, suggesting no cross-resistance with either R1479 (4'-azidocytidine) or 2'-C-methyl nucleosides. Pharmacokinetic studies with RO-9187 in rats and dogs showed that plasma concentrations exceeding HCV replicon IC(50) values 8-150-fold could be achieved by low dose (10 mg/kg) oral administration. Therefore, 2'-alpha-deoxy-4'-azido nucleosides are a new class of antiviral nucleosides with promising preclinical properties as potential medicines for the treatment of HCV infection.
| Targets |
HCV(IC50=171 nM)
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|---|---|
| ln Vitro |
RO-9187 is phosphorylated with efficiencies up to three times higher than deoxycytidine, making it a great substrate for deoxycytidine kinase. Inhibiting RNA synthesis by HCV polymerases from HCV genotypes 1a and 1b or with S96T or S282T point mutations with comparable potencies, RO-9187 suggests that there is no cross-resistance with 2′-C-methyl nucleosides or R1479 (4′-azidocytidine). RO-9187-TP production rose in a dose- and time-dependent fashion. Half-maximum triphosphate formation is reached at 12 μM, and the maximum triphosphate concentration at 24 hours is 87 pmol/106 cells. RO-9187 [1].
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| ln Vivo |
Following oral dosing, rats' plasma exposures to RO-9187 rise between 10 and 2000 mg/kg in a dose-dependent manner. At a dose level of 10 mg/kg, rats and dogs exhibit plasma concentrations of 1.4 and 26 μM (390 and 7454 ng/mL), respectively. Rats given 2000 mg/kg/day can achieve plasma concentrations of up to 57 μM[1].
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| Animal Protocol |
Rats: Hanover-Wistar rats are used in a 2-week oral range finding toxicity study with RO-9187 and ribavirin. For 14 days, five male and five female rats in each of the five treatment groups receive once-daily oral gavage doses of 200, 600, or 2000 mg/kg RO-9187 or 200 mg/kg ribavirin[1].
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| References |
| Molecular Formula |
C9H12N6O5
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|---|---|
| Molecular Weight |
284.22878
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| Exact Mass |
284.09
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| Elemental Analysis |
C, 38.03; H, 4.26; N, 29.57; O, 28.14
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| CAS # |
876708-03-1
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| Appearance |
Solid powder
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| SMILES |
O=C1N=C(N)C=CN1[C@H]2[C@@H](O)[C@H](O)[C@](CO)(N=[N+]=[N-])O2
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| InChi Key |
ODLGMSQBFONGNG-XZMZPDFPSA-N
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| InChi Code |
InChI=1S/C9H12N6O5/c10-4-1-2-15(8(19)12-4)7-5(17)6(18)9(3-16,20-7)13-14-11/h1-2,5-7,16-18H,3H2,(H2,10,12,19)/t5-,6-,7+,9+/m0/s1
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| Chemical Name |
4-amino-1-[(2R,3S,4S,5R)-5-azido-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one
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| Synonyms |
RO-9187; RO 9187; RO9187.
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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) |
DMSO : ~100 mg/mL (~351.83 mM)
H2O : ~5 mg/mL (~17.59 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (8.80 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
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 (8.80 mM) 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; with ultrasonication. 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. View More
Solubility in Formulation 3: 2.5 mg/mL (8.80 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: 2.5 mg/mL (8.80 mM) Solubility in Formulation 5: 5.88 mg/mL (20.69 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C). |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5183 mL | 17.5914 mL | 35.1828 mL | |
| 5 mM | 0.7037 mL | 3.5183 mL | 7.0366 mL | |
| 10 mM | 0.3518 mL | 1.7591 mL | 3.5183 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.
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