SML1953

GDC-0879

≥98% (HPLC)

• 別名: 1H-Inden-1-one, 2,3-dihydro-5-[1-(2-hydroxyethyl)-3-(4-pyridinyl)-1H-pyrazol-4-yl]-, oxime, 2,3-Dihydro-5-[1-(2-hydroxyethyl)-3-(4-pyridinyl)-1H-pyrazol-4-yl]-1H-inden-1-one oxime, 2-[4-[(1E)-1-(Hydroxyimino)-2,3-dihydro-1H-inden-5-yl]-3-(pyridine-4-yl)-1H-pyrazol-1-yl]ethan-1-ol, 5-(1-(2-Hydroxyethyl)-3-(pyridin-4-yl)-1H-pyrazol-4-yl)-2,3-dihydro-1H-inden-1-one oxime, AR00341677, GDC0879
• 実験式（ヒル表記法）: C₁₉H₁₈N₄O₂
• CAS番号: 905281-76-7
• 分子量: 334.37
• MDL番号: MFCD16875916
• UNSPSCコード: 12352200
• NACRES: NA.77

特性

• 品質水準: 100
• アッセイ: ≥98% (HPLC)
• 形状: powder
• 色: white to beige
• 溶解性: DMSO: 2 mg/mL, clear (warmed)
• 保管温度: 2-8°C
• SMILES記法: OCCN(N=C1C2=CC=NC=C2)C=C1C3=CC=C4C(CC/C4=N\O)=C3
• InChI: 1S/C19H18N4O2/c24-10-9-23-12-17(19(21-23)13-5-7-20-8-6-13)15-1-3-16-14(11-15)2-4-18(16)22-25/h1,3,5-8,11-12,24-25H,2,4,9-10H2/b22-18+
• InChI Key: DEZZLWQELQORIU-RELWKKBWSA-N

詳細

生物化学的／生理学的作用

GDC-0879 (AR00341677) is an orally active, ATP site-targeting, highly potent Raf inhibitor (IC50 against V600E B-Raf-catalyzed MEK phophorylation = 0.13 nM with 4 μM ATP; IC50 against pERK in V600E B-Raf-expressing cells = 29 nM/Colo205, 59 nM/A375, 63 nM/Malme-3M) with great selectivity over >200 protein kinases (IC50 >1 μM). Oral administration is shown to effectively suppress Colo205 and A375 xenografts-derived tumor growth and pMEK1 in mice in vivo (35 mg/kg bid; 50-200 mg/kg qd or bid). Paradoxically, GDC-0879 also induces wild-type and enhances V600E B-Raf dimerization in an allosteric manner independent of kinase activity inhibition, resulting in selective anti-proliferation activity against V600E B-Raf cancer cells, but not in KRAS mutant or RAS/WT Raf cells, where GDC-0879 induces formation of B–C and A–B heterodimers and downstream signaling activation.

安全性情報

• 保管分類コード: 11 - Combustible Solids
• WGK: WGK 3
• 引火点(°F): Not applicable
• 引火点(℃): Not applicable