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受注：045-509-1970 |
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化学情報
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Synonyms | zoledronate monohydrate, CGP-4244 monohydrate | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C5H10N2O7P2.H2O |
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| 分子量 | 290.1 | CAS No. | 165800-06-6 | |
| Solubility (25°C)* | 体外 | 0.5MNAOH | 6.02 mg/mL (20.75 mM) | |
| Water | 2.3 mg/mL (7.92 mM) | |||
| DMSO | 0.01 mg/mL (0.03 mM) | |||
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
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溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | Zoledronic acid (Zoledronate, CGP-4244) monohydrate, a nitrogen-containing bisphosphonate, is a potent osteoclast inhibitor which 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. |
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| in vitro | Zoledronic acid inhibits osteoclast maturation indirectly by increasing OPG protein secretion and decreasing transmembrane RANKL expression in human osteoblasts. Treatment of primary human OB‐like cells with the potent nitrogen-containing BP, zoledronic acid (ZOL), resulted in a downregulation of membrane-ssociated RANKL protein expression. In addition to direct effects on cells of the osteoclast lineage, zoledronic acid may inhibit bone resorption by reducing transmembrane RANKL expression and increasing OPG secretion in osteoclast (OB)-like cells[1]. Zoledronic acid induces growth inhibition (IC50:10–50 μM) and apoptotic death of human pancreatic cancer cells. The proapoptotic effect was correlated to cleavage/activation of caspase-9 and poly(ADP)-ribose polymerase, but not of caspase-3. It interferes with growth and survival pathways downstream to p21ras[2]. Zoledronic acid is also a potent inhibitor of angiogenesis. In vitro, zoledronic acid inhibits proliferation of human endothelial cells stimulated with fetal calf serum, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (IC50 values 4.1, 4.2, and 6.9 μM, respectively), and modulates endothelial cell adhesion and migration. In cultured aortic rings and in the chicken egg chorioallantoic membrane assay, zoledronic acid reduces vessel sprouting. ZOL also exerted a concentration-dependent, biphasic effect on the adhesion and migration of HUVEC in vitro. ZOL concentrations of 1 and 3 μM increased cell adhesion but inhibited it at 30 and 100 μM. Similarly, cell migration was stimulated by 0.3 to 10 μM ZOL, whereas 30 μM completely inhibited it. These findings suggest that ZOL could interfere with cytoskeletal function in endothelial cells[4]. |
| in vivo | Zoledronic acid affects breast cancer metastasis to visceral organs as well as bone[3]. When administered systemically to mice, zoledronic acid potently inhibits the angiogenesis induced by subcutaneous implants impregnated with bFGF [ED50, 3 μg/kg (7.5 nmol/kg) s.c.][4]. In nice transplanted with osteosarcoma (OS) cells, ZOL administration prevented osteolysis and significantly reduced the amount of OS-induced bone formation while has no effect on tumor burden at the primary site. ZOL failed to reduce lung metastasis and in some cases was associated with larger and more numerous metastatic lesions[5]. |
プロトコル(参考用のみ)
| 細胞アッセイ | 細胞株 | human PC cell lines (BxPC-3, CFPAC-1 and PANC-1) |
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| 濃度 | 1-100 μM | |
| 反応時間 | 72 h | |
| 実験の流れ | 'BxPC-3 and CFPAC-1 are adherent human pancreatic adenocarcinoma cell lines that were grown in RPMI 1640 and Iscove's modified Dulbecco's media, respectively. PANC-1 is a human epithelioid pancreas carcinoma cell line that was grown in Dulbecco's modified Eagle's medium (DMEM). All media were supplemented with 10% heat-inactivated fetal bovine serum, 2 mM L-glutamine, 100 μg/ml streptomycin and 100 U/ml penicillin. All PC cell lines were cultured at a constant temperature of 37°C in a humidified atmosphere of 5% carbon dioxide (CO2). The neutralised sodium salt of ZOL was dissolved in sterile ddH2O and used at a final concentration in a range of 1-100 μM. Analysis of cell proliferation was performed on PC cells in the presence of increasing concentrations of ZOL by the MTT assay. Briefly, PC cells (3 × 104/well) were seeded in 96-well plates in serum-containing media and allowed to attach for 24 h. The medium was then removed and replaced with new medium containing ZOL at different concentrations. Cells were incubated under these conditions for a time course spanning 72 h. Then cells were incubated with 10 μl well−1 of thiazolyl blue (MTT, 5 mg/ml) for 1 h at 37°C. After incubation, 100 μl of 0.04 N HCl in isopropanol was added into each well and the absorbance was measured at a wavelength of 620 nm in a microplate reader. |
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| 動物実験 | 動物モデル | Female mice (strain Tiflbm:MAG) |
| 投薬量 | 1, 10 and 100 μg/kg | |
| 投与方法 | s.c. |
参考
Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：
| Targeting of colorectal cancer organoids with zoledronic acid conjugated to the anti-EGFR antibody cetuximab [ J Immunother Cancer, 2022, 10(12)e005660] | PubMed: 36543375 |
| Estrogen Responsive Gene MAST4 Regulates Myeloma Bone Disease [ J Bone Miner Res, 2022, 10.1002/jbmr.4507] | PubMed: 35064934 |
| CD155 and CD112 as possible therapeutic targets of FLT3 inhibitors for acute myeloid leukemia [ Oncol Lett, 2022, 23(2):51] | PubMed: 34992684 |
| Establishment of a 3D model of tumor-driven angiogenesis to study the effects of anti-angiogenic drugs on pericyte recruitment [ Biomater Sci, 2021, 10.1039/d0bm02107e] | PubMed: 34136892 |
| Classic and Targeted Anti-Leukaemic Agents Interfere With the Cholesterol Biogenesis Metagene in Acute Myeloid Leukaemia: Therapeutic Implications [ J Cell Mol Med, 2020, 25] | PubMed: 32450611 |
| Nanoformulated Zoledronic Acid Boosts the Vδ2 T Cell Immunotherapeutic Potential in Colorectal Cancer. [ Cancers (Basel), 2020, 31;12(1) pii: E104] | PubMed: 31906080 |
| Zoledronic acid re‑sensitises gefitinib‑resistant lung cancer cells by inhibiting the JAK/STAT3 signalling pathway and reversing epithelial‑mesenchymal transition [ Oncol Rep, 2020, 45(2):459-468] | PubMed: 33416163 |
| The BTLA and PD-1 signaling pathways independently regulate the proliferation and cytotoxicity of human peripheral blood γδ T cells [ Immun Inflamm Dis, 2020, 10.1002/iid3.390] | PubMed: 33332777 |
| The effects of mechanically loaded osteocytes and inflammation on bone remodeling in a bisphosphonate-induced environment [ Bone, 2019, 127:460-473] | PubMed: 31301402 |
| A Bone Anabolic Effect of RANKL in a Murine Model of Osteoporosis Mediated Through FoxP3+ CD8 T Cells [ J Bone Miner Res, 2015, 30(8):1508-22] | PubMed: 25656537 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。