Donafenib (Sorafenib D3)

製品コードS9621 バッチS962101

印刷

化学情報

Synonyms

Bay 43-9006 D3, CM-4307

Storage
(From the date of receipt)

3 years -20°C powder

化学式

C₂₁H₁₃D₃ClF₃N₄O₃

分子量

467.84

CAS No.

1130115-44-4

Solubility (25°C)*

体外

DMSO

94 mg/mL (200.92 mM)

Ethanol

6 mg/mL (12.82 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	2.3mg/ml	Taking the 1 mL working solution as an example, add 50 μL of 46 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil	4.75mg/ml	Taking the 1 mL working solution as an example, add 50 μL of 95 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

* <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	Donafenib (Sorafenib D3, Bay 43-9006 D3, CM-4307) is the deuterium labeled Sorafenib. Sorafenib is a multikinase inhibitor IC50s of 6 nM, 15 nM, 20 nM and 22 nM for Raf-1, mVEGFR-2, mVEGFR-3 and B-RAF, respectively.
in vitro	BAY 43-9006 suppresses both wild-type and V599E mutant BRAF activity in vitro. In addition, BAY 43-9006 demonstrates significant activity against several receptor tyrosine kinases involved in neovascularization and tumor progression, including vascular endothelial growth factor receptor (VEGFR)-2, VEGFR-3, platelet-derived growth factor receptor β, Flt-3, and c-KIT. In cellular mechanistic assays, BAY 43-9006 demonstrates inhibition of the mitogen-activated protein kinase pathway in colon, pancreatic, and breast tumor cell lines expressing mutant KRAS or wild-type or mutant BRAF, whereas non–small-cell lung cancer cell lines expressing mutant KRAS are insensitive to inhibition of the mitogen-activated protein kinase pathway by BAY 43-9006. Potent inhibition of VEGFR-2, platelet-derived growth factor receptor β, and VEGFR-3 cellular receptor autophosphorylation is also observed for BAY 43-9006.^[1]
in vivo	Once daily oral dosing of BAY 43-9006 demonstrates broad-spectrum antitumor activity in colon, breast, and non–small-cell lung cancer xenograft models. Immunohistochemistry demonstrates a close association between inhibition of tumor growth and inhibition of the extracellular signal-regulated kinases (ERKs) 1/2 phosphorylation in two of three xenograft models examined, consistent with inhibition of the RAF/MEK/ERK pathway in some but not all models. Additional analyses of microvessel density and microvessel area in the same tumor sections using antimurine CD31 antibodies demonstrates significant inhibition of neovascularization in all three of the xenograft models.^[1]

プロトコル(参考用のみ)

細胞アッセイ	細胞株	MDA-MB-231, Colo-205, HT-29, DLD-1, NCI-H460, A549 cell lines
	濃度	0.01 μM, 0.03 μM, 0.1 μM, 0.3 μM, 1 μM, 3 μM
	反応時間	120 min
	実験の流れ	Tumor cell lines are plated at 2 × 10⁵ cells per well in 12-well tissue culture plates in DMEM growth media (10% heat-inactivated FCS) overnight. Cells are washed once with serum-free media and incubated in DMEM supplemented with 0.1% fatty acid-free BSA containing various concentrations of Donafenib (Sorafenib D3, BAY 43-9006) in 0.1% DMSO for 120 minutes to measure changes in basal pMEK 1/2, pERK 1/2, or pPKB. Cells are washed with cold PBS (PBS containing 0.1 mmol/L vanadate) and lysed in a 1% (v/v) Triton X-100 solution containing protease inhibitors. Lysates are clarified by centrifugation, subjected to SDS-PAGE, transferred to nitrocellulose membranes, blocked in TBS-BSA, and probed with anti-pMEK 1/2 (Ser²¹⁷/Ser²²¹; 1:1000), anti-MEK 1/2, anti-pERK 1/2 (Thr²⁰²/Tyr²⁰⁴; 1:1000), anti-ERK 1/2, anti-pPKB (Ser⁴⁷³; 1:1000), or anti-PKB primary antibodies. Blots are developed with horseradish peroxidase (HRP)-conjugated secondary antibodies and developed with Amersham ECL reagent on Amersham Hyperfilm.
動物実験	動物モデル	Female NCr-nu/nu mice
	投薬量	7.5 mg/kg, 15 mg/kg, 30 mg/kg, 60 mg/kg
	投与方法	Oral gavage

参考

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。