Fosbretabulin (Combretastatin A4 Phosphate) Disodium

製品コードS7204 バッチS720401

印刷

化学情報

Chemical Structure 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 28 mg/mL (63.59 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.

溶剤液（一定の濃度）を調合する

生物活性

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.

プロトコル(参考用のみ)

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.

カスタマーフィードバック

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]

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：

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。

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