ASP5878 是具有口服活性的、FGFR 1、2、3、和 4的抑制剂，其对FGFR 1、2、3、和 4 激酶的IC50值分别为 0.47 nM、0.6 nM、0.74 nM 和 3.5 nM。ASP5878 具有潜在的抗肿瘤活性。
| 生物活性 | ASP5878 is an oral active inhibitor ofFGFR1, 2, 3, and 4, withIC50values of 0.47 nM, 0.6 nM, 0.74 nM and 3.5 nM forFGFR1, 2, 3, and 4 kinase activity. ASP5878 has potential antineoplastic activity[1]. |
| IC50& Target | FGFR1 0.47 nM (IC50) | FGFR2 0.6 nM (IC50) | FGFR3 0.74 nM (IC50) | FGFR4 3.5 nM (IC50) |
|
体外研究
(In Vitro) | ASP5878 shows potent antiproliferative activity in most human HCC cell lines[1].
ASP5878 inhibits FGFR4 phosphorylation in a concentration-dependent manner. ASP5878 treatment results in the suppression of phosphorylation, mobility shift of FRS2, and suppression of ERK phosphorylation[1].
Cell Viability Assay[1] | Cell Line: | Human HCC cell lines. | | Concentration: | 0-1000 nM. | | Incubation Time: | 5 days. | | Result: | HuH-7, Hep3B2.1-7, and JHH-7 cell lines exhibited potent sensitivity to ASP5878, with IC50values of 27, 8.5, and 21 nmol/L, respectively.
The growth inhibition rate of HLF was 64% and those of other ASP5878-sensitive cell lines were higher than 95% at 1000 nM. |
|
体内研究
(In Vivo) | ASP5878 (3 mg/kg, orally, once daily) shows antitumor activity in a Hep3B2.1-7 subcutaneous xenograft and HCC orthotopic xenograft mouse model[1].
ASP5878 induces shrinkage of FGF19-expressing HCC xenograft model[1].
| Animal Model: | Four-week-old male nude mice (CAnN.Cg-Foxn1nu/CrlCrlj [nu/nu]) (Hep3B2.1-7 cells inoculated subcutaneously)[1]. | | Dosage: | 3 mg/kg. | | Administration: | Orally once daily from days 14 to 52. | | Result: | Induced tumor regression by 9% and 88% at 1 and 3 mg/kg, respectively, without affecting the body weight for 14 days.
Induced the suppression of FGFR4 phosphorylation, mobility shift of FRS2, and suppression of ERK phosphorylation. |
| Animal Model: | HCC orthotopic xenograft model (mouse)[1]. | | Dosage: | 3 mg/kg. | | Administration: | Orally once daily for 24 days. | | Result: | Exhibited a lower tumor burden than vehicle- and sorafenibtreated mice.
Induced sustained tumor regression without tumor regrowth. |
|
| Clinical Trial | |
| 分子量 | |
| 性状 | |
| Formula | |
| CAS 号 | |
| 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 |
|
| 溶解性数据 | In Vitro: DMSO : ≥ 250 mg/mL(613.69 mM) *"≥" means soluble, but saturation unknown. 配制储备液 | 1 mM | 2.4548 mL | 12.2739 mL | 24.5477 mL | | 5 mM | 0.4910 mL | 2.4548 mL | 4.9095 mL | | 10 mM | 0.2455 mL | 1.2274 mL | 2.4548 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℃, 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 (5.11 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (5.11 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%corn oil Solubility: ≥ 2.08 mg/mL (5.11 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (5.11 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。
|
m.cnreagent.com