受注:045-509-1970 |
技術サポート:[email protected] 平日9:00〜18:00 1営業日以内にご連絡を差し上げます |
Synonyms | CA 4DP | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
|
化学式 | C18H19O8P.2Na |
|||
分子量 | 440.29 | CAS No. | 168555-66-6 | |
Solubility (25°C)* | 体外 | Water | 49 mg/mL (111.29 mM) | |
DMSO | Insoluble | |||
Ethanol | Insoluble | |||
* <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. |
製品説明 | Fosbretabulin (Combretastatin A4 Phosphate) Disodium is the water-soluble prodrug of Combretastatin A4 (CA4), which is a microtubule-targeting agent that binds β-tubulin with Kd of 0.4 μM in a cell-free assay. Fosbretabulin Disodium inhibits the polymerization of tubulin with IC50 of 2.4 μM, and also disrupts tumor vasculature. Fosbretabulin disodium induces mitotic arrest and apoptosis in endothelial cells. Phase 3. |
---|---|
in vitro | Fosbretabulin disodium (Combretastatin A-4 phosphate disodium, CA4P disodium) is the water-soluble prodrug of combretastatin A4 (CA4), which is originally isolated from African tree Combretum caffrum. CA4 is a tubulin-binding agent that binds at or near the colchicine binding site of β-tubulin (Kd = 0.40 μM), inhibits tubulin assembly with IC50 of 2.4 μM. [1] CA4 is cytotoxic towards proliferating but not quiescent endothelial cells, has potent and selective toxicity towards tumor vasculature. [2] CA4P (1 mM, 30 minutes) disrupts the endothelial microtubule cytoskeleton and mediates changes in endothelial cell morphology. CA4P stimulates actin stress fiber formation and membrane blebbing and increases monolayer permeability via Rho/Rho-kinase. [3] CA4P increases endothelial cell permeability, while inhibiting endothelial cell migration and capillary tube formation predominantly through disruption of VE-cadherin/β-catenin/Akt signaling pathway, thereby leading to rapid vascular collapse and tumor necrosis. [4] |
in vivo | CA4P causes rapid, extensive and irreversible vascular shutdown in experimental tumor models following the administration of a single dose at 10% of the maximum tolerated dose (MTD). CA4P causes a 93% reduction in vascular volume 6 h following drug administration. [2] CA4P(100 mg/kg, 6 h following administration) reduces tumor blood by approximately 100-fold, compared with approximately 7-fold in the spleen. [5] |
特徴 | A microtubule associated inhibitor with higher affinity to β-tubulin vs. Colchicine. Best for advanced solid tumors, anaplastic thyroid cancer, & choroidal neovascularization. |
キナーゼアッセイ | Tubulin assembly-disassembly | |
---|---|---|
The assembly of microtubules from isolated tubulin is carried out spectrophotometrically at 350 nm and utilises the increase in turbidity which is associated with microtubule formation. Assembly is initiated by temperature increase from 10 to 35 °C. The effect of drugs on the increase in light absorption is carried. Drugs are dissolved in DMSO (<4%), which does not affect control assembly | ||
細胞アッセイ | 細胞株 | HUVECs |
濃度 | ~50 nM | |
反応時間 | 12-48 h | |
実験の流れ | For the proliferation assay, the minimal concentration of FBS (1%) diluted in X-VIVO medium is used to allow sufficient viability of endothelial cells. After detachment, the cells are seeded at a concentration of 2×104 HUVECs in each well of 24-well plates, allowed to adhere overnight, and then incubated with or without cytokines (5 ng/ml FGF-2 or 5 ng/ml VEGF-A). CA4P is added at 0 – 50 nM. After incubation for 12, 24, 36, and 48 hours, cells are detached by trypsin/EDTA and manually counted using trypan blue exclusion. |
|
動物実験 | 動物モデル | BD9 rats implanted with tumor |
投薬量 | 100 mg/kg, 3 ml/kg | |
投与方法 | i.p. |
Data from [Data independently produced by , , Transl Oncol, 2018, 11(5):1251-1258]
Data from [Data independently produced by , , Res Vet Sci, 2017, 112:222-228]
Data from [Data independently produced by , , Res Vet Sci, 2018, 122:1-6]
Antitumor effect of anti-vascular therapy with STING agonist depends on the tumor microenvironment context [ Front Oncol, 2023, 13:1249524] | PubMed: 37655095 |
Antitumor effect of anti-vascular therapy with STING agonist depends on the tumor microenvironment context [ Front Oncol, 2023, 13:1249524] | PubMed: 37655095 |
The Global Phosphorylation Landscape of SARS-CoV-2 Infection [ Cell, 2020, 182(3):685-712.e19] | PubMed: 32645325 |
The Global Phosphorylation Landscape of SARS-CoV-2 Infection [ Cell, 2020, 182(3):685-712.e19] | PubMed: 32645325 |
Salmonella enterica Typhimurium engineered for nontoxic systemic colonization of autochthonous tumors [ J Drug Target, 2020, 10.1080/1061186X.2020.1818759] | PubMed: 32886538 |
Power Doppler ultrasound and contrast-enhanced ultrasound demonstrate non-invasive tumour vascular response to anti-vascular therapy in canine cancer patients [ Sci Rep, 2019, 9(1):9262] | PubMed: 31239493 |
Noninvasive Anatomical and Functional Imaging of Orthotopic Glioblastoma Development and Therapy using Multispectral Optoacoustic Tomography [Balasundaram G, et al. Transl Oncol, 2018, 11(5):1251-1258] | PubMed: 30103155 |
7α,8α-Epoxynagilactones and their glucosides from the twigs of Podocarpus nagi: Isolation, structures, and cytotoxic activities [ Fitoterapia, 2018, 125:174-183] | PubMed: 29355751 |
Vascular disrupting effect of combretastatin A-4 phosphate with inhibition of vascular endothelial cadherin in canine osteosarcoma-xenografted mice [Izumi Y, et al. Res Vet Sci, 2018, 122:1-6] | PubMed: 30439557 |
A dose‐escalation study of combretastatin A4‐phosphate in healthy dogs [Abma E, et al. Vet Comp Oncol, 2018, 16(1):E16-E22] | PubMed: 28620942 |
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。