GNE-9815|cas:2729996-45-4|西域试剂

GNE-9815,98.28%

产品编号：Bellancom-142160| CAS NO：2729996-45-4| 分子式：C₂₆H₂₂FN₅O₂| 分子量：455.48

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货号	价格	库存与货期
Bellancom-142160	￥3500.00	杭州北京（现货）
Bellancom-142160	￥6000.00	杭州北京（现货）
Bellancom-142160	￥11500.00	杭州北京（现货）

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GNE-9815

产品介绍

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 K_i 值分别为 0.062 和 0.19 nM。GNE-9815 联合 MEK 抑制剂 Cobimetinib (HY-13064) 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。

生物活性

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.

体外研究

GNE-9815 shows synergistic activity in KRAS mutant A549 and HCT116 cancer cells in combination with the MEK inhibitor Cobimetinib.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

体内研究

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.

西域 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).

体内研究

西域 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).

性状

Solid

溶解性数据

In Vitro:

DMSO : 50 mg/mL (109.77 mM; ultrasonic and warming and heat to 80°C)

配制储备液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	2.1955 mL	10.9774 mL	21.9549 mL
5 mM	0.4391 mL	2.1955 mL	4.3910 mL
10 mM	0.2195 mL	1.0977 mL	2.1955 mL

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.

请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% saline
Solubility: ≥ 2.5 mg/mL (5.49 mM); Clear solution

此方案可获得 ≥ 2.5 mg/mL (5.49 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。
将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液
2.

请依序添加每种溶剂： 10% DMSO 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.5 mg/mL (5.49 mM); Clear solution

此方案可获得 ≥ 2.5 mg/mL (5.49 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
3.

请依序添加每种溶剂： 10% DMSO 90% corn oil
Solubility: ≥ 2.5 mg/mL (5.49 mM); Clear solution

此方案可获得 ≥ 2.5 mg/mL (5.49 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。
以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。