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).

>98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

阿仑膦酸钠；Alendronate；MK 217；G-704650 Adronat

white solid

DMSO ：20 mg/mL (61.3 mM) with gentle warming
Water ：20 mg/mL (61.3 mM) with gentle warming

Alendronate, acting directly on osteoclasts, inhibits a rate-limiting step in the cholesterol biosynthesis pathway, essential for osteoclast function. Alendronate inhibits the isoprenoid biosynthesis pathway and interferes with protein prenylation, as a result of reduced geranylgeranyl diphosphate levels. Alendronate inhibits the incorporation of mevalonolactone into proteins of 18-25 kDa and into nonsaponifiable lipids, including sterols in osteoclasts. Alendronate causes a dose-dependent inhibition of MVA incorporation into sterols and a concomitant increase in incorporation of radiolabel into IPP and DMAPP.

Alendronate causes erosions in the rabbit stomach, but not antral ulceration in rats. Alendronate increases the incidence and size of indomethacin-induced antral ulcers. Alendronate also enhances indomethacin-induced gastricdamage in the rat, and delayed gastric ulcer healing. Alendronate (0.04-0.1 mg/kg twice weekly or 0.1 mg/kg weekly) partially blocks the establishment of bone metastases by human PC-3 ML cells and results in tumor formation in the peritoneum and other soft tissues. Alendronate pretreatment of mice (0.1 mg/kg twice weekly or weekly) and dosing along with taxol (10-50 mg/kg/day, twice weekly, or weekly) blocks the growth of PC-3 ML tumors in the bone marrow and soft tissues in a statistically significant manner and improves survival rates significantly by 4-5 weeks.