BLU9931 是一种有效的，高度选择性的，不可逆的成纤维细胞生长因子受体 4 (FGFR4) 抑制剂，其IC50值为 3 nM，Kd值为 6 nM。BLU9931 具有显着的抗肿瘤活性。
| 生物活性 | BLU9931 is a potent, highly selective, and irreversiblefibroblast growth factorreceptor 4 (FGFR4)inhibitor with anIC50of 3 nM and aKdof 6 nM. BLU9931 has significant antitumor activity[1]. |
| IC50& Target | FGFR1 591 nM (IC50) | FGFR2 493 nM (IC50) | FGFR3 150 nM (IC50) | FGFR4 3 nM (IC50) |
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体外研究
(In Vitro) | BLU9931 inhibits proliferation of HCC cell lines that express an intact FGFR4 signaling complex, withEC50s of 0.07 μM, 0.11 μM and 0.02 μM for Hep 3B, HuH7 and JHH7 cells, respectively[1].
BLU9931 (0.3-300 nM; 1 hour; MDA-MB-453 and Hep 3B cells) treatment demonstrates potent, dose-dependent reduction of phosphorylation of FGFR4 signaling pathway components, including fibroblast growth factor receptor substrate 2 (FRS2), MAPK, and AKT in MDA-MB-453 cells. BLU9931 shows dose-dependent inhibition of the signaling cascade downstream of FGFR4. BLU9931 exhibits potent inhibition of phosphorylation of the FGFR4 pathway components in Hep 3B cells. BLU9931 treatment leads to induction of caspase-3/7 activity, indicative of induction of apoptosis that results in inhibition of signaling downstream of FGFR4[1].
BLU9931 (100 nM; 0 -24 hours; Hep 3B cells) treatment increases CYP7A1 mRNA expression and the expression of the proliferative marker EGR1 is inhibited[1].
Western Blot Analysis[1] | Cell Line: | MDA-MB-453 and Hep 3B cells | | Concentration: | 0.3 nM, 1 nM, 3 nM, 10 nM, 30 nM, 100 nM, 300 nM | | Incubation Time: | 1 hour | | Result: | Demonstrated potent, dose-dependent reduction of phosphorylation of FGFR4 signaling pathway components, including fibroblast growth factor receptor substrate 2 (FRS2), MAPK, and AKT in MDA-MB-453 and Hep 3B cells. |
RT-PCR[1] | Cell Line: | Hep 3B cells | | Concentration: | 100 nM | | Incubation Time: | 0 hour, 4 hours, 8 hour, 24 hours | | Result: | Increased CYP7A1 mRNA expression. And the expression of the proliferative marker EGR1 was inhibited. |
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体内研究
(In Vivo) | BLU9931 (10-100 mg/kg; oral administration; twice every day; for 21 days; mice) treatment demonstrates antitumor activity in HCC xenograft models[1].
| Animal Model: | Mice injected with Hep 3B cells[1] | | Dosage: | 10 mg/kg, 30 mg/kg or 100 mg/kg | | Administration: | Oral administration; twice every day; for 21 days | | Result: | Resulted in dose-dependent growth inhibition of Hep 3B tumors. Prevented weight loss in a dose-dependent manner. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 125 mg/mL(245.40 mM;Need ultrasonic) 配制储备液 | 1 mM | 1.9632 mL | 9.8159 mL | 19.6317 mL | | 5 mM | 0.3926 mL | 1.9632 mL | 3.9263 mL | | 10 mM | 0.1963 mL | 0.9816 mL | 1.9632 mL |
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储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 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: ≥ 2.08 mg/mL (4.08 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.08 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.8 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。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.08 mg/mL (4.08 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.08 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (4.08 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.08 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 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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