GSK983 blocks RNA virus replication with EC50 values of 10–40 nM, and also blocks cell proliferation. GSK983 acts by inhibition of dihydroorotate dehydrogenase (DHODH), necesssary for pyrimidine biosynthesis. Exogenous deoxycytidine was able to reduce GSK983 cytotoxicity, allowing cells to synthesize DNA, but still preventing RNA virus replication. GSK983 was active against dengue fever and Venezuelan equine encephalitis viruses.
| Molecular Weight | 325.79 |
| Formula | C18H16ClN3O |
| CAS Number | 827591-02-6 |
| Solubility (25°C) | DMSO: 10 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
[5] Robert Harvey, et al. GSK983: a novel compound with broad-spectrum antiviral activity
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