TAK-733 化学構造
分子量: 504.23

品質と確認

カスタマーレビュー(3)

Quality Control & MSDS

製品情報

  • Compare MEK Inhibitors
    MEK阻害剤を比較
  • 研究分野
  • Combination Therapy
    併用療法
  • TAK-733のメカニズム

製品の説明

生物活性

情報 TAK-733は、強力な、選択的な、ATP-非競争的MEKアロステリック部位阻害剤で、IC50 が 3.2nMです。
目標 MEK1
IC50 3.2 nM [1]
In vitro試験 TAK-733 is highly potent and selective MEK allosteric site inhibitor with IC50 of 3.2 nM. TAK-733 shows potent enzymatic and cell activity with an EC50 of 1.9 nM against ERK phosphorylation in cells. [1]
In vivo試験 TAK-733 demonstrates broad antitumor activity in mouse xenograft models of human cancer including models of melanoma, colorectal, NSCLC, pancreatic and breast cancer. TAK-733 is well tolerated with pharmacokinetics and pharmacodynamics that support once-daily oral dosing in humans. [1] TAK-733 shows maximally efficacious doses at once daily orally doses of 10 mg/kg. [2]
臨床試験 A Multicenter, Open-label, Dose-escalation, Phase I Study of TAK-733, an Oral MEK Inhibitor, in Adult Patients With Advanced Nonhematologic Malignancies.
特集

推薦された実験操作 (公開の文献だけ)

動物実験: [2]

動物モデル Human solid tumor xenograft models including NSCLC (NCI H23 [KRAS and LKB1 mutations]), CRC (SW620 [KRAS, APC, p53 mutations]) Pancreatic cancer (Panc 1 and Capan 1 [KRAS mutations] and BxPC-3 [No MAPK mutations]) models in immunocompromised mice.
製剤 Saline
投薬量 10 mg/kg
管理 Orally administrated once daily for 21 days

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 TAK-733 SDF
分子量 504.23
化学式

C17H15F2IN4O4

CAS No. 1035555-63-5
保管 2年-20℃
6月-80℃in DMSO
別名
溶解度 (25°C) * In vitro DMSO 101 mg/mL (200.3 mM)
<1 mg/mL (<1 mM)
エタノール <1 mg/mL (<1 mM)
* <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 (R)-3-(2,3-dihydroxypropyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione

研究分野

カスタマーレビュー (3)


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Rating
Source , , Dr.Wang from Southern Medical Hospital . TAK-733 purchased from Selleck
Method Western blot
Cell Lines A549 cells
Concentrations 0-10 uM
Incubation Time 2 h
Results Effect of MEK inhibitor TAK-733 in A549 cells. A549 cells were incubated with increasing concentrations of TAK-733 for 2 h. The cell lysates were harvested and phosphorylation of indicated proteins was determined by Western blotting.

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Rating
Source Jonas Nilsson, PhD from University of Gothenburg. TAK-733 purchased from Selleck
Method Western blot, cell apoptosis assays
Cell Lines Mouse carcinoma cells
Concentrations 1-1000 nM
Incubation Time 16/40 h
Results (A) whereas apoptosis was induced at 40h. (B) Biological effects of the compounds correlated with effects on phosphorylation of the MEK target ERK. (C) IC50 on S-phase and ERK-posphorylation: TAK-733=1-10 nM, GSK1120212=<1 nM.

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Rating
Source Dr. Zhang of Tianjin Medical University. TAK-733 purchased from Selleck
Method Western blot
Cell Lines T47D cells
Concentrations 0-10 μM
Incubation Time 3 h
Results Reduction of ERK1/2 phosphorylation in T47D cells treated with TAK-733 was observed.

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。

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