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PD 173074

现货
Catalog No.
A8253
FGFR抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 600.00
现货
10mg
¥ 500.00
现货
50mg
¥ 1,400.00
现货

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Background

PD173074 is a poten and selective fibroblast growth factor receptor (FGFR) inhibitor. Fibroblast growth factor-2 is reported to be able to induce proliferation and chemoresistance in Small cell lung cancer (SCLC) cells.

In vitro: PD173074 was found to block H-510 and H-69 SCLC proliferation and clonogenic growth in a dose-dependent fashion and prevent FGF-2-induced chemoresistance as well. These effects correlate with the inhibition of both FGFR1 and FGFR2 transphosphorylation. In addition, PD173074 showed a high degree of selectivity for FGFR tyrosine kinase [2].

In vivo: In the H-510 xenograft mouse model, tumor growth was significanlty improved similar to that seen with single-agent cisplatin administration. Accordingly, PD173074 treatment resulted in significanlty prolonged median survival when compared with that of control sham-treated animals. More dramatically, PD173074 also induced complete responses lasting >6 months in 50% of in mice H-69 xenografts [2].

Clinical trial: PD173074 is still in the preclinical development stage, and no clinical data are available currently.

References:
[1] Pardo OE, Latigo J, Jeffery RE, Nye E, Poulsom R, Spencer-Dene B, Lemoine NR, Stamp GW, Aboagye EO, Seckl MJ.  The fibroblast growth factor receptor inhibitor PD173074 blocks small cell lung cancer growth in vitro and in vivo. Cancer Res. 2009 Nov 15;69(22):8645-51.
[2] Mohammadi M, Froum S, Hamby JM, Schroeder MC, Panek RL, Lu GH, Eliseenkova AV, Green D, Schlessinger J, Hubbard SR.  Crystal structure of an angiogenesis inhibitor bound to the FGF receptor tyrosine kinase domain. EMBO J. 1998 Oct 15;17(20):5896-904.

Chemical Properties

Physical AppearanceA solid
StorageStore at 4°C
M.Wt523.67
Cas No.219580-11-7
FormulaC28H41N7O3
SynonymsPD 173074,PD-173074
Solubility≥26.1835mg/mL in DMSO, ≥108.4 mg/mL in EtOH with ultrasonic, <2.8 mg/mL in H2O
Chemical Name1-tert-butyl-3-[2-[4-(diethylamino)butylamino]-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl]urea
SDFDownload SDF
Canonical SMILESCCN(CC)CCCCNC1=NC2=NC(=C(C=C2C=N1)C3=CC(=CC(=C3)OC)OC)NC(=O)NC(C)(C)C
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

激酶实验 [1]:

体外激酶抑制试验

使用全长FGFR-1激酶,在100 μL反应体系中进行试验。上述反应体系含25 mM HEPES缓冲液 (pH 7.4),150 mM NaCl,10 mM MnCl2,0.2 mM原钒酸钠,750 μg/mL谷氨酸和酪氨酸共聚物 (4:1),各种浓度的PD 173074,和60 ~ 75 ng酶。加入[γ-32P]ATP(每次孵育需要含0.4 μCi [γ-32P]ATP的5 μM ATP)开始反应,将样品置于25 °C下孵育10分钟。加入30%三氯乙酸,将材料沉淀到玻璃纤维滤垫上,终止上述反应。用15%三氯乙酸将过滤膜洗涤3次,使用WALLAC1250 betaplate计数器测定过滤膜的放射性,计算掺入到谷氨酸酪氨酸聚合物底物的[32P]量。

细胞实验 [1]:

细胞系

NIH 3T3细胞

制备方法

在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20 °C可放置数月。

反应条件

0 ~ 1000 nM;5分钟

实验结果

PD 173074呈剂量依赖性地抑制FGFR1自磷酸化,其IC50值为1 ~ 5 nM。此外,PD 173074也抑制VEGFR2自磷酸化,其IC50值为100 ~ 200 nM。

动物实验 [1]:

动物模型

诱导角膜新生血管的Swiss Webster小鼠模型

给药剂量

1或2 mg/kg/day;腹腔注射

实验结果

在1或2 mg/kg/day的剂量下,PD 173074呈剂量依赖性地显着抑制由FGF或VEGF诱导的血管生成。此外,PD 173074没有显著的毒性。

其它注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. Mohammadi M, Froum S, Hamby JM, Schroeder MC, Panek RL, Lu GH, Eliseenkova AV, Green D, Schlessinger J, Hubbard SR. Crystal structure of an angiogenesis inhibitor bound to the FGF receptor tyrosine kinase domain. EMBO J. 1998 Oct 15;17(20):5896-904.

生物活性

Description PD173074是一种强效的FGFR1抑制剂,IC50值约为25 nM,同时抑制VEGFR2,IC50值为100-200 nM,对FGFR1的选择性比PDGFR及c-Src高约1000倍。
靶点 FGFR1 VEGFR2        
IC50 ~25 nM 100-200 nM        

质量控制

化学结构

PD 173074

相关生物数据

PD 173074

相关生物数据

PD 173074