Alendronate (Fosamax) is a farnesyl diphosphate synthase inhibitor with IC50 of 460 nM. It is a nitrogen-containing bisphosphate that acts as a robust inhibitor of bone resorption and induces apoptosis in osteoclasts. It causes disruption of the ruffled border and actin cytoskeleton of osteoclasts and induces in vitro apoptosis of osteoclasts and macrophages by inhibiting farnesyl diphosphate synthase (IC50 = 460 nM). It efficiently chelates metal ions and functions as a broad-spectrum MMP inhibitor (IC50 ~ 40 - 70 uM). And it also displays antimetastatic, anti-invasive and cell-adhesion-promoting properties (IC50 ~ 1 pM, in vitro invasion of prostate cancer cells).
| Molecular Weight | 326.13 |
| Formula | C4H13NO7P2.3H2O.Na |
| CAS Number | 121268-17-5 |
| Solubility (25°C) | Water 10 mg/mL warmed |
| 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.
[1] Gennady Ananchenko, et al. Alendronate sodium
[2] W P Olszynski, et al. Alendronate for the treatment of osteoporosis in men
[3] Neil A Reynolds, et al. Alendronate/colecalciferol
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