AMG-208 化学構造
分子量: 383.4

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Quality Control & MSDS

製品説明

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    c-Met製品生物活性の比較
  • 研究分野

製品の説明

生物活性

製品説明 AMG-208は、9.3nMのIC50による非常に選択的なc-Met阻害剤です。
ターゲット c-Met
IC50 9 nM [1]
In vitro試験 AMG-208 shows the potent inhibition of kinase c-Met activity with IC50 of 9 nM in a cell-free assay. Besides, AMG-208 treatment also leads to the inhibition of HGF-mediated c-Met phosphorylation in PC3 cells with IC50 of 46 nM. [1] Incubation of AMG-208 with rat and human liver microsomes in the presence of NADPH qualitatively yields C6-phenylarene oxidation products as the major metabolites. [1] Pre-incubation of AMG-208 with human liver microsomes for 30 minutes shows a potent time-dependent inhibition for CYP3A4 metabolic activity with IC50 of 4.1 μM, which is an eightfold decrease relative to the IC50 (32 μM) without preincubation. [2] AMG-208 is identified to be a c-MET and RON dual selective inhibitor. [3]
In vivo試験 In male Sprague−Dawley rats, AMG-208 (0.5 mg/kg i.v.) shows a high bioavailability with Cl of 0.37 L/h/kg, Vss of 0.38 L/kg and T1/2 of 1 hour, while AMG-208 (2 mg/kg i.v.) shows a bioavailability with AUC0→∞ of 2517 ng·h/mL and F of 43%, respectively. [1]
臨床試験 AMG-208 is currently in Phase I clinical trials in patients with Advanced Solid Tumors.
特集

プロトコル (参考用のみ)

キナーゼアッセイ: [1]

In Vitro Kinase Assay IC50 measurements versus c-Met kinase and its mutants are determined using homogenous time-resolved fluorescence (HTRF) assays. AMG-208 is tested in a 10-point dose-response curve for each enzyme using an ATP concentration of two-thirds Km for each. Most assays consists of enzyme mixed with kinase reaction buffer [20 mM Tris-HCl (pH 7.5), 10 mM MgCl2, 5 mM MnCl2, 100 mM NaCl, 1.5 mM EGTA]. A final concentration of 1 mM DTT, 0.2 mM NaVO4, and 20 μg/mL BSA is added before each assay. For all assays, 5.75 mg/mL streptavidin-allophycocyanin and 0.1125 nM Eu-PT66 are added immediately before the HTRF reaction. Plates are incubated for 30 minutes at room temperature and read on a Discovery instrument Molecules are tested in a 10-point serial dilution for each c-Met construct using an ATP concentration of two thirds Km value that is determined for each enzyme preparation and calculated using the Eadie-Hofstee and Lineweaver-Burke methods.

動物実験: [1]

動物モデル Male Sprague-Dawley rats
製剤 AMG-208 is dissolved in DMSO.
投薬量 ≤2 mg/kg
投与方法 Administered via i.v. and p.o.

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

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)0.020.151.80.40.0810312
Body Surface Area (m2)0.0070.0250.150.050.020.50.240.6
Km factor361285201220
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 AMG-208 SDF
分子量 383.4
化学式

C22H17N5O2

CAS No. 1002304-34-8
保管 2年-20℃
6月-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 0.25 mg/mL (0.65 mM)
<1 mg/mL (<1 mM)
エタノール <1 mg/mL (<1 mM)
In vivo 1% DMSO/30% polyethylene glycol/1% Tween 80 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 7-methoxy-4-((6-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy)quinoline

技術サポート&よくある質問(FAQ)

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