GNE-9815
规格
| Cas Number | 2729996-45-4 |
| 规格或纯度 | ≥98% |
| 纯度 | ≥98% |
| 包装 | 50mg 或 10mg 或 5mg 或 25mg |
产品信息
| 品牌 | 阿拉丁 |
| 溶解性 | DMSO : 50 mg/mL (109.77 mM; ultrasonic and warming and heat to 80°C) |
| 过滤标签 | Raf,MAPK/ERK Pathway |
| 储存温度 | -20°C储存 |
| 运输条件 | 超低温冰袋运输 |
| 生化和生理学机理 | GNE-9815（化合物 7）是一种高选择性的泛 RAF 抑制剂，具有良好的口服生物利用度。GNE-9815 对 CRAF 和 BRAF 的 K i 值分别为 0.062 和 0.19 nM。GNE-9815 与 MEK 抑制剂 Cobimetinib ( HY-13064 ) 联用可显示出协同作用。 |
| 英文描述 |
GNE-9815 (compound 7) is a highly selective, pan- RAF inhibitor with good oral bioavailability. GNE-9815 exhibits K i values of 0.062 and 0.19 nM for CRAF and BRAF , respectively. GNE-9815 combines with MEK inhibitor Cobimetinib ( HY-13064 ) shows synergistic modulation of MAPK pathway. GNE-9815 can be used in studies of KRAS mutant cancers In Vitro GNE-9815 shows synergistic activity in KRAS mutant A549 and HCT116 cancer cells in combination with the MEK inhibitor Cobimetinib. MCE has not independently confirmed the accuracy of these methods. They are for reference only. In Vivo GNE-9815 (15 mg/kg; p.o.; single) demonstrates synergistic MAPK pathway modulation when combines with the MEK inhibitor Cobimetinib in an HCT116 xenograft mouse model . GNE-9815 (5 mg/kg; p.o.; single) shows good oral bioavailability and (1 mg/kg; i.v.; single) exhibits low blood clearance, moderate volume of distribution, and short half-life . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Female NCR nude mice (6 to 8-week-old; 24-26 g; HCT116 xenograft mice model) . Dosage: 15 mg/kg Administration: Intravenous injection or oral administration; single. Result: Resulted in pathway inhibition as demonstrated by partial inhibition of pRSK between 2 and 24 h, but more robust, albeit transient, inhibition of the downstream MAPK target genes, DUSP6 and SPRY4. Led to deeper inhibition of the downstream MAPK target genes DUSP6 and SPRY4, when combined with the MEK inhibitor Cobimetinib, with maximal inhibition at 8 h and with a more modest rebound in levels at 24 h, post final dose. Animal Model: Female NCR nude mice (6 to 8-week-old; 24-26 g) . Dosage: 1 mg/kg (for i.v.); 5 mg/kg (for p.o.). Administration: Intravenous injection or oral administration; single. Result: Exhibited CL b , V dss and t 1/2 values of 17 mL/min∙kg, 1.7 L/kg and 1.9 h, respectively. Showed good oral bioavailability with F% of 37%. (methylcellulose/Tween formulation). Form:Solid IC50& Target:CRAF 0.062 nM (Ki) Braf 0.19 nM (Ki) |