AZ 628

AZ 628は力なチロシン・タンパク質阻害剤、 野生のタイプCRAFと BRAF V600Eに作用すると、 IC50 がそれぞれ 29 nM と 34 nMになる。

目録号S2746
価格 在庫  
USD 189 In stock
USD 340 In stock
USD 592 In stock

AZ 628 化学構造
分子量: 451.52

品質と確認

Quality Control & MSDS

製品情報

  • Compare Raf Inhibitors
    Raf阻害剤を比較
  • 研究分野

製品の説明

生物活性

情報 AZ 628は力なチロシン・タンパク質阻害剤、 野生のタイプCRAFと BRAF V600Eに作用すると、 IC50 がそれぞれ 29 nM と 34 nMになる。
目標 wild-type CRAF BRAFV600E wild-type BRAF
IC50 29 nM 34 nM 100 nM [1]
In vitro試験 AZ628 prevents activation of number of tyrosine protein kinases including VEGFR2, DDR2, Lyn, Flt1, FMS and others. AZ628 suppresses anchorage-dependent and -independent growth, gives rise to cell cycle arrest, and induces apoptosis in colon and melanoma cell lines harboring B-RafV600E mutation. The profile of AZ628 cross-reactivity suggests that similar to sorafenib, AZ628 may be antiangiogenic based on prevention of VEGFR2. [1] AZ628-resistant clones are approximately 100-fold more resistant to AZ628 than the parental cell line, exhibiting IC50 of approximately 10 μM, compared with 0.1 μM for the parental cell line. Effective suppression of p-ERK1/2 levels is observed in the M14 parental cell line following treatment with increasing concentrations of AZ628. AZ628-resistant clones express elevated CRAF. Elevated CRAF expression is a potential mechanism of acquired resistance to continuous AZ628 exposure, resulting in sustained activation of ERK1/2. p-ERK1/2 activity is not significantly inhibited by exposure to AZ628 in one of these three AZ628-insensitive cell lines (Wm1552C). Unlike in the AZ628-resistant M14 cells in which AZ628 fails to suppress the activation of ERK, AZ628 treatment efficiently attenuates ERK activation in the NRAS mutant melanoma cells.[2]
In vivo試験
臨床試験
特集

推薦された実験操作 (公開の文献だけ)

細胞アッセイ: [1]

細胞系 M14 expressing the V600E BRAF mutation
濃度 0.01-10 μM
処理時間 Overnight
方法 Approximately 0.5-2.5 × 105 M14 cells are seeded in 12 or 24 - well plates, respectively, in medium supplemented with 5% FBS. After overnight incubation, the cells are treated with various concentrations of AZ628. Fresh medium and drug is replaced every 2 days until the untreated control wells reached confluence. At this time-point, the media is removed and the cells are fixed in 4% formaldehyde in PBS for 20 minutes at room temperature. Cells are then washed twice with PBS and stained with a 1:5000 solution of the fluorescent nucleic acid stain Syto60. Quantitation of fluorescent signal intensity is carried out at 700 nm, using an Odyssey Infrared Imager. Each experiment is performed in quadruplicate and the results shown represent the average of the four values compared to untreated wells. Error bars represent standard deviation of the 4 values from the mean. High-throughput cell growth/viability assays are performed.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesBaboonDogMonkeyRabbitGuinea pigRatHamsterMouse
Weight (kg)121031.80.40.150.080.02
Body Surface Area (m2)0.60.50.240.150.050.0250.020.007
Km factor202012128653
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

参考

化学情報

Download AZ 628 SDF
分子量 451.52
化学式

C27H25N5O2

CAS No. 878739-06-1
保管 2年-20℃
6月-80℃in DMSO
別名
溶解度 (25°C) * In vitro DMSO 90 mg/mL (199 mM)
<1 mg/mL (<1 mM)
エタノール <1 mg/mL (<1 mM)
In vivo 30% PEG400/0.5% Tween80/5% propylene glycol, 30 mg/mL
* <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.
化学名 3-(2-cyanopropan-2-yl)-N-(4-methyl-3-(3-methyl-4-oxo-3,4-dihydroquinazolin-6-ylamino)phenyl)benzamide

研究分野

製品表彰状 (1)

技術サポート&よくある質問(FAQ)

顧客がするかもしれない質問に対する答えは、指示を取り扱っている阻害剤で見つかります。話題は、貯蔵液(阻害剤と特別な注意を細胞ベースの分析法と動物のために必要とする問題を保存することは実験します)を準備する方法を含みます。

電話番号: +1-832-582-8158 Ext:3月曜日〜金曜日 9:00 AM–5:00 PM (米国中部標準時)

他の問い合わせをするならば、メッセージを残してください。

* 必須

Related Raf 阻害剤

  • CEP-32496

    CEP-32496 は RAF 阻害剤で、BRAF(V600E)、BRAF(WT)、 CRAF、Abl-1 、 CSF-1R に作用すると、IC50 がそれぞれ 14 nM、 36 nM、 39 nM、 3 nM 、 9 nMです。

    Features:对BRAF(V600E)突变型和相关的c-Raf具有高的结合亲和力,而对MAPK通路的其它关键激酶,包括MEK-1,MEK-2,ERK-1和ERK-2无显著的亲和力。

  • Encorafenib (LGX818)

    Encorafenib (LGX818) is a potent and selective BRAFV600E kinase inhibitor with IC50 of 0.3 nM.

  • TAK-632

    TAK-632 is a potent pan-Raf inhibitor with IC50 of 8.3 nM and 1.4 nM for B-Raf(wt) and C-Raf, respectively, showing less or no inhibition against other tested kinases.

  • Sorafenib

    Sorafenib is a multikinase inhibitor of Raf-1, B-Raf and VEGFR-2 with IC50 of 6 nM, 22 nM and 90 nM, respectively.

  • Vemurafenib (PLX4032, RG7204)

    Vemurafenib (PLX4032, RG7204)新しくて強力な阻害剤で、 B-RAFV600Eに作用すると、IC50 が 31 nMになる。

    Features:PLX4032是新型有效的B-RAFV600E 肿瘤蛋白抑制剂。

  • Dabrafenib (GSK2118436)

    Dabrafenib(GSK2118436)は、B-Rafの強力なATP競争的阻害剤で、 B-Raf、 B-RafV600E 、c-Rafに作用する時、 IC50 がそれぞれ 3.2 nM、 0.8 nM 、 5.0 nMです。

  • Sorafenib Tosylate

    Sorafenib Tosylateは、Raf-1、B-RafとVEGFR-2のマルチキナーゼ阻害剤で、IC50 がそれぞれ 6 nM、 22 nM、90 nMです。

  • PLX-4720

    PLX-4720は、B-Raf(V600E)とc-Raf-1(Y340D/Y341D)の「実行中の」形の強力で選択的な阻害剤で、IC50 がそれぞれ 13 nM と 6.7 nMです。

  • GDC-0879

    GDC-0879 は新型有効の選択B-Raf阻害剤、精製のB-RafV600E酵素や細胞p-ERKを作用すると、IC50がそれぞれ0.13 nM と 63 nMとなる.

最近見られたアイテム

Tags: AZ 628を買う | AZ 628供給者 | AZ 628を購入する | AZ 628費用 | AZ 628生産者 | オーダーAZ 628 | AZ 628代理店
お問い合わせ