GDC-0879 化学構造
分子量: 334.37

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Quality Control & MSDS

製品説明

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製品の説明

生物活性

製品説明 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.
ターゲット B-Raf
IC50 0.13 nM [1]
In vitro試験 GDC-0879 also inhibits cellular pERK with IC50 of 63 nM. GDC-0879 shows comparable potency in A375 melanoma and Colo205 colorectal carcinoma cell lines, both of which are B-RafV600E mutant, with IC50 of 59 nM and 29 nM for pMEK1 inhibition respectively. GDC-0879 potently inhibits B-RafV600E in Malme3M cells with IC50 of 0.75 μM. GDC-0879 also shows EC50 values < 0.5 μM in many tumor cells (A375, 624, SK-MEL-28, Malme3M, C32, 928, 888, G-361, Colo205, Colo206, SW1417, CL34, and Colo201). [1]
In vivo試験 In GDC-0879 treated mice, both cell line- and patient-derived BRAFV600E tumors exhibit stronger and more sustained pharmacodynamic inhibition (>90% for 8 hours) and improved survival compared to mutant KRAS-expressing tumors. Although there is involvement of activated RAF signaling in RAS-induced tumorigenesis, decreased time to progression is observed for some KRAS-mutant tumors following GDC-0879 administration. Whereas GDC-0879-mediated efficacy is associated strictly with B-RafV600E status, MEK inhibition also attenuates proliferation and tumor growth of cell lines expressing wild-type BRAF (81% KRAS mutant, 38% KRAS wild type). The responsiveness of B-RafV600E melanoma cells to GDC-0879 could be dramatically altered by pharmacologic and genetic modulation of PI3K pathway activity. [2]
臨床試験
特集

プロトコル (参考用のみ)

動物実験: [2]

動物モデル Female nu/nu mice
製剤 0.5% methylcellulose/0.2% Tween 80
投薬量 100 mg/kg
投与方法 Oral gavage

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 GDC-0879 SDF
分子量 334.37
化学式

C19H18N4O2

CAS No. 905281-76-7
保管 2年-20℃
6月-80℃in solvent
別名 AR-00341677
溶解度 (25°C) * In vitro DMSO 66 mg/mL warming (197.38 mM)
エタノール 5 mg/mL (14.95 mM)
<1 mg/mL (<1 mM)
In vivo 0.5% methylcellulose+0.2% 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 (E)-5-(1-(2-hydroxyethyl)-3-(pyridin-4-yl)-1H-pyrazol-4-yl)-2,3-dihydroinden-1-one oxime

文献中の引用 (13)

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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