Zoledronic acid (Zoledronate; CGP-42446; CGP42446A; ZOL-446; Zometa; Reclast) is potent bisphosphonate with anti-bone-resorption activity. It induces apoptosis in osteoclasts by inhibiting enzymes of the mevalonate pathway and preventing the isoprenylation of small GTP-binding proteins such as Ras and Rho. Zoledronic acid is an approved medication used to treat various bone diseases such as osteoporosis, high blood calcium due to cancer, bone breakdown
due to cancer, Paget's disease of bone and Duchenne muscular dystrophy. Zoledronic acid is a synthetic imidazole bisphosphonate analog of pyrophosphate with anti-bone-resorption activity. As a third-generation bisphosphonate, zoledronic acid binds to hydroxyapatite crystals in the bone matrix, slowing their dissolution and inhibiting the formation and aggregation of these crystals.
理化性质和储存条件
| Molecular Weight (MW) | 272.09 |
|---|
| Formula | C5H10N2O7P2 |
|---|
| CAS No. | 118072-93-8 |
|---|
| Storage | -20℃ for 3 years in powder form |
|---|
| -80℃ for 2 years in solvent |
| Solubility (In vitro) | DMSO: < 1 mg/mL |
|---|
| Water: < 1 mg/mL |
| Ethanol: < 1 mg/mL |
| Solubility (In vivo) | 30% PEG400+0.5% Tween80+5% Propylene glycol: 10 mg/mL |
|---|
| Synonyms | CGP42446; CGP42446A; ZOL446; CGP-42446; CGP-42446A; ZOL-446; CGP 42446; CGP 42446A; ZOL 446; Zoledronate, trade names: Zometa; Reclast. |
|---|
实验参考方法
| In Vitro | In vitro activity: Zoledronic acid at doses of 2.0 and 4.0 mg and pamidronate at a dose of 90 mg each significantly reduced the need for radiation therapy to bone (P < 0.05) in contrast with 0.4 mg zoledronic acid, which did not. Skeletal-related events of any kind, pathologic fractures, and hypercalcemia also occurred less frequently in patients treated with 2.0 or 4.0 mg zoledronic acid or pamidronate than with 0.4 mg zoledronic acid. Zoledronic acid administration may be a potentially valuable adjunct to distraction osteogenesis treatment, to enhance bone strength, thus reducing refracture complications. Zoledronic acid, a more recent drug, was compared with pamidronic acid in two clinical trials, but the results are unconvincing because of the unusually poor performance of pamidronic acid. Safety of zoledronic acid is uncertain, owing to a lack of long-term data.
Cell Assay: Zoledronic acid(CGP 42446; ZOL 446) is an activator of protein kinase C with apoptotic effects on multiple myeloma cell lines. It inhibited proliferation of human foetal osteoblastic cell line (hFOB) with an IC50 of 40 uM. |
|---|
| In Vivo | Zoledronic acid (120 mg/kg, s.c.) prevents the formation of lesions, prevents cancellous bone loss and loss of bone mineral density, and reduces osteoclast perimeter in 5T2MM-bearing mice. Zoledronic acid (120 mg/kg, s.c.) also decreases paraprotein concentration, decreases tumor burden, and reduces angiogenesis in 5T2MM-bearing mice. |
|---|
| Animal model | Mice |
|---|
| Formulation & Dosage | 120 mg/kg, s.c. |
|---|
| References | Cancer. 2001 Apr 1;91(7):1191-200; Clin Biomech (Bristol, Avon). 2002 Nov-Dec;17(9-10):716-8. |
|---|
m.cnreagent.com