GNE-9815 (化合物 7) 是一种高选择性的、具有较好口服生物利用度的泛型 RAF 抑制剂，其对 CRAF 和 BRAF 的 Ki 值分别为 0.062 和 0.19 nM。GNE-9815 联合 MEK 抑制剂 Cobimetinib 显示出协同调节 MAPK 途径的作用。GNE-9815 可用于 KRAS 突变型癌症的研究。$
| Cas No. | 2729996-45-4 |
| 分子式 | C26H22FN5O2 |
| 分子量 | 455.48 |
| 溶解度 | DMSO : 50 mg/mL (109.77 mM; ultrasonic and warming and heat to 80°C) |
| 储存条件 | Store at -20°C |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while. |
| Shipping Condition | Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request |
| 产品描述 | GNE-9815 (compound 7) is a highly selective, pan-RAFinhibitor with good oral bioavailability. GNE-9815 exhibitsKivalues of 0.062 and 0.19 nM forCRAFandBRAF, respectively. GNE-9815 combines withMEKinhibitorCobimetinibshows synergistic modulation ofMAPKpathway. GNE-9815 can be used in studies ofKRASmutant cancers[1]. GNE-9815 shows synergistic activity in KRAS mutant A549 and HCT116 cancer cells in combination with the MEK inhibitor Cobimetinib[1]. 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[1].
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[1]. | Animal Model: | Female NCR nude mice (6 to 8-week-old; 24-26 g; HCT116 xenograft mice model)[1]. | | 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)[1]. | | Dosage: | 1 mg/kg (for i.v.); 5 mg/kg (for p.o.). | | Administration: | Intravenous injection or oral administration; single. | | Result: | Exhibited CLb, Vdssand t1/2values 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). |
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