产品号 #73572_C
骨吸收抑制剂；抑制法呢基二磷酸（FPP）合成酶
总览
唑来膦酸（Zoledronic Acid）是一种含氮双膦酸盐，可抑制法呢基二磷酸（FPP）合酶（IC₅₀=5 nM），从而阻止蛋白质异戊烯化和破骨细胞介导的骨吸收（Dunford et al.）。此外，它对羟基磷灰石 (Ki=3.5 μM) 具有高亲和力，可直接与矿化骨结合（Nancollas et al.）。本产品以分子水合物形式提供。
癌症研究
·抑制多种癌细胞系的增殖、血管生成和骨粘附（Li & Davis; Zekri et al.）。
·体外抑制乳腺癌和前列腺癌细胞侵袭（Boissier et al.; Li & Davis）。
·体外诱导破骨细胞瘤细胞凋亡（Benford et al.）。
细胞类型
癌细胞及细胞系
种属
人，小鼠，非人灵长类，其它细胞系，大鼠
CAS 编号
165800-06-6
化学式
C₅H₁₀N₂O₇P₂ · H₂O
纯度
≥ 95 %
靶点
FPP合酶
Protocols and Documentation
Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.
Resources and Publications
Educational Materials (1)
Publications (6)
The anti-tumour effects of zoledronic acid. Journal of bone oncology 2014 MAR
Abstract
Bone is the most common site for metastasis in patients with solid tumours. Bisphosphonates are an effective treatment for preventing skeletal related events and preserving quality of life in these patients. Zoledronic acid (ZA) is the most potent osteoclast inhibitor and is licensed for the treatment of bone metastases. Clodronate and pamidronate are also licensed for this indication. In addition, ZA has been demonstrated to exhibit antitumour effect. Direct and indirect mechanisms of anti-tumour effect have been postulated and at many times proven. Evidence exists that ZA antitumour effect is mediated through inhibition of tumour cells proliferation, induction of apoptosis, synergistic/additive to inhibitory effect of cytotoxic agents, inhibition of angiogenesis, decrease tumour cells adhesion to bone, decrease tumour cells invasion and migration, disorganization of cell cytoskeleton and activation of specific cellular antitumour immune response. There is also clinical evidence from clinical trials that ZA improved long term survival outcome in cancer patients with and without bone metastases. In this review we highlight the preclinical and clinical studies investigating the antitumour effect of bisphosphonates with particular reference to ZA.
Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite. Bone 2006
Abstract
Bisphosphonates are now the most widely used drugs for diseases associated with increased bone resorption, such as osteoporosis. Although bisphosphonates act directly on osteoclasts, and interfere with specific biochemical processes such as protein prenylation, their ability to adsorb to bone mineral also contributes to their potency and duration of action. The aim of the present study was to compare the binding affinities for hydroxyapatite (HAP) of 6 bisphosphonates currently used clinically and to determine the effects of these bisphosphonates on other mineral surface properties including zeta potential and interfacial tension. Affinity constants (K(L)) for the adsorption of bisphosphonates were calculated from kinetic studies on HAP crystal growth using a constant composition method at 37 degrees C and at physiological ionic strength (0.15 M). Under conditions likely to simulate bisphosphonate binding onto bone, there were significant differences in K(L) among the bisphosphonates for HAP growth (pH 7.4) with a rank order of zoledronate textgreater alendronate textgreater ibandronate textgreater risedronate textgreater etidronate textgreater clodronate. The measurements of zeta potential show that the crystal surface is modified by the adsorption of bisphosphonates in a manner best explained by molecular charges related to the protonation of their side-chain moieties, with risedronate showing substantial differences from alendronate, ibandronate, and zoledronate. The studies of the solid/liquid interfacial properties show additional differences among the bisphosphonates that may influence their mechanisms for binding and inhibiting crystal growth and dissolution. The observed differences in kinetic binding affinities, HAP zeta potentials, and interfacial tension are likely to contribute to the biological properties of the various bisphosphonates. In particular, these binding properties may contribute to differences in uptake and persistence in bone and the reversibility of effects. These properties, therefore, have potential clinical implications that may be important in understanding differences among potent bisphosphonates, such as the apparently more prolonged duration of action of alendronate and zoledronate compared with the more readily reversible effects of etidronate and risedronate.
Zoledronic acid: a new parenteral bisphosphonate. Clinical therapeutics 2003 NOV
Abstract
BACKGROUND Inhibition of bone resorption using bisphosphonates is an important step in palliation of complications of advanced cancer, such as hypercalcemia and metastatic bone disease. OBJECTIVE The goal of this article was to describe the pharmacologic properties of zoledronic acid (zoledronate) and discuss findings from preclinical and clinical studies of its use in skeletal disorders. METHODS Relevant English-language literature was identified using the terms zoledronic acid, zoledronate, Zometa, and 118072-93-8 through searches of MEDLINE (1966-June 2003) and International Pharmaceutical Abstracts (1970-June 2003), and abstract proceedings from the American Society of Clinical Oncology (1997-2002). RESULTS Zoledronic acid is a nitrogen-containing bisphosphonate that inhibits bone resorption. It is indicated for the treatment of hypercalcemia of malignancy and for the treatment of patients with multiple myeloma or documented metastasis from solid tumors, in conjunction with standard antineoplastic therapy. The recommended dosage is 4 mg via IV over textgreateror= 15 minutes every 3 or 4 weeks. Compared with pamidronate 90 mg, zoledronic acid 4 and 8 mg provided a higher complete response rate for hypercalcemia of malignancy by day 10 (88.4% and 86.7% vs 69.7%; P = 0.002 and P = 0.015) and longer duration of action (median time to relapse, 30 and 40 days vs 17 days; P = 0.001 and P = 0.007). In patients with breast cancer or multiple myeloma, zoledronic acid was as effective as pamidronate in delaying time to a first skeletal-related event (373 days vs 363 days). In patients with hormone-refractory prostate cancer and bone metastases, zoledronic acid 4 mg reduced the proportion of patients who experienced a skeletal-related event (33% vs 44% with placebo; P = 0.021) or a skeletal fracture (13% vs 22% with placebo; P = 0.015). In patients with bone metastases from solid tumors, zoledronic acid delayed the median time to a first skeletal-related event (230 days vs 163 days with placebo; P = 0.023). Common adverse events include fever, nausea, constipation, fatigue, and bone pain. CONCLUSION Zoledronic acid is an effective and generally well-tolerated treatment for hypercalcemia of malignancy and skeletal complications of metastatic bone disease.
更多信息
| Species | Human, Mouse, Non-Human Primate, Other, Rat |
|---|---|
| Cas Number | 165800-06-6 |
| Chemical Formula | C₅H₁₀N₂O₇P₂ · H₂O |
| Purity | ≥ 95% |
| Target | FPP Synthase |
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