TH-Z93, a lipophilic bisphosphonate, is an FPPS inhibitor (IC50 = 90 nM). TH-Z93 exhibits potent efficacy, increasing both antibody titers and avidity. TH-Z93 exhibited strong prophylactic effects in a pathogenic influenza model. Importantly, co-administration of GGPP during vaccination (by-passing GGPPS inhibition) with any of the three MVA pathway inhibitors (simvastatin, TH-Z93, and TH-Z145) abolished all of the adjuvant effects in mice.
| Molecular Weight | 368.26 |
| Formula | C12H22N2O7P2 |
| CAS Number | 2260887-09-8 |
| Solubility (25°C) | Water ~1 mg/mL (ultrasonic and warming and adjust pH to 10 with NaOH) |
| 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.
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