Ibandronate (Sodium)

Ibandronate Sodium is an orally active, selective inhibitor of farnesyl pyrophosphate synthase (FPP synthase). Ibandronate Sodium can block the mevalonate pathway to inhibit the isoprenylation modification of small GTPases (such as RAS, RHO family proteins), induce tumor cell apoptosis and inhibit bone resorption. Ibandronate Sodium inhibits tumor cell proliferation (such as ER+ breast cancer cells), promotes the expression of the pro-apoptotic gene FAS, and can produce synergistic anti-tumor effects with anti-estrogen compounds. Ibandronate Sodium is used in the study of osteoporosis and bone metastatic tumors (such as breast cancer bone metastasis)^[1][2][3][4]. In Vitro:Ibandronate Sodium (10-6-10-3 M; 3 d) inhibits cell growth in a dose-dependent manner, induces apoptosis, and completely counteractes the pro-proliferative effect of 17β-estradiol in ER⁺ breast cancer cell lines MCF-7, IBEP-2, and ER^- cell line MDA-MB-231^[1].
Ibandronate Sodium (1-200 μM; 72 h) inhibits cell viability, activated caspase 3/7 and 8, upregulates the expression of the pro-apoptotic gene FAS, and downregulates the DNA methyltransferase DNMT1 in human U-2 osteosarcoma and mouse CCL-51 breast cancer cells, and FAS siRNA could partially reverse its growth inhibitory effect^[2].
In Vivo:Ibandronate (1 mg/kg; intravenous injection; once every 3 weeks; a total of 9 times) Sodium does not cause cumulative renal damage in rats, only induces a mild degree of proximal tubular degeneration and single cell necrosis, and the biochemical parameters are not significantly different from the control group^[3].
Ibandronate (1 μg/kg/day; oral; 1 week of administration/2-6 weeks of withdrawal; 22 weeks-1 year) Sodium effectively prevents castration-induced bone loss in the female ovariectomized (OVX) rat model, maintaines bone mass, bone structure and biomechanical strength, and the effects of intermittent and continuous administration are equivalent^[4].
Ibandronate (65 μg/kg/day; oral; 2 weeks on/11 weeks off; 1 year) Sodium dose-dependently increases bone volume in female ovariohysterectomized (OHX) beagle dogs, completely reverses castration-induced bone loss and restores bone density to control levels^[4].
Ibandronate (10-150 μg/kg; intravenous injection; once a month; 16 months) Sodium dose-dependently prevents bone loss at the lumbar spine and femoral neck in female ovariectomized cynomolgus monkeys, with the highest dose restoring bone density to sham-operated group levels, and has no adverse effects on bone mineralization and healing^[4].