Alendronate sodium hydrate

Alendronate sodium hydrate (Alendronate; MK 217; G-704650 Adronat) is a bisphosphonate that acts as a specific inhibitor of osteoclastmediated bone resorption, inhibits osteoclast protein-tyrosine phosphatase (PTPepsilon) with IC50 of 2 uM; also inhibits the activities of other bacterially expressed PTPs such as PTPsigma and CD45, suppresses in vitro formation of multinucleated osteoclasts from osteoclast precursors and in vitro bone resorption by isolated rat osteoclasts with IC50 of 10 uM; also is also inhibits farnesyl disphosphate synthase with IC50 of 1.7 uM.Osteoporosis Approved (In Vitro) :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 [3H]mevalonolactone into proteins of 18-25 kDa and into nonsaponifiable lipids, including sterols in osteoclasts. Alendronate causes a dose-dependent inhibition of [3H]MVA incorporation into sterols and a concomitant increase in incorporation of radiolabel into IPP and DMAPP. (In Vivo) :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 delays 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.