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AXL1717

现货
Catalog No.
A3209
IGF-1R抑制剂,口服有效。
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 950.00
现货
10mg
¥ 870.00
现货
50mg
¥ 3,080.00
现货
250mg
¥ 13,370.00
Ship with 10-15 days

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Background

AXL1717 (Picropodophyllotoxin) is a selective inhibitor of IGF-1R with IC50 value rangs from 0.24-0.33 μM [1].
IGF-1R (type 1 insulin-like growth factor receptor) is a transmembrane receptor that activated by IGF-1 and plays an important role in cell growth and anabolic effects in adults. It has been reported that over-expression of IGF-1R is correlated with a variety of cancers and its inhibitors has been revealed to anti-cancer in clinical study [1] [2].
AXL 1717 is a potent IGF-1RTK inhibitor and has ability to inhibit tumor cells combined with HDAC inhibitor LBH589. When tested with 4 human myeloma cells (RPMI 8226, Karpas707, LP-1, and OPM-2) and 1 murine cell (5T33MM), AXL1717 treatment markedly decreased cell survival in a dose-dependent manner, arrested cell cycle in G2-M phase and induced cell apoptosis by inhibiting IGF-1RTK [1]. In four colon carcinoma cell lines (HT-29, HCT-116, DLD-1 and CaCO-2), AXL1717 treatment showed high ability to inhibit cell proliferation and migration in a dose-dependent manner [2].
In mouse model with 5TMM subcutaneous xenograft, administration of AXL 1717 (1.5 mg/d) resulted in a prolonged survival in combination with LBH (2.5 mg/kg/d) compared with control group [1].
AXL1717 has been tested to treat non-small cell lung cancer patients in a Phase I/II clinically [3].
References:
[1].Lemaire, M., et al., The HDAC inhibitor LBH589 enhances the antimyeloma effects of the IGF-1RTK inhibitor picropodophyllin. Clin Cancer Res, 2012. 18(8): p. 2230-9.
[2].Feng, X., et al., Multiple antitumor effects of picropodophyllin in colon carcinoma cell lines: clinical implications. Int J Oncol, 2012. 40(4): p. 1251-8.
[3].Ekman, S., et al., Clinical Phase I study with an Insulin-like Growth Factor-1 receptor inhibitor: experiences in patients with squamous non-small cell lung carcinoma. Acta Oncol, 2011. 50(3): p. 441-7.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt414.41
Cas No.477-47-4
FormulaC22H22O8
SynonymsPicropodophyllotoxin;Picropodophyllin;PPP;AXL-1717;AXL 1717
Solubility≥20.7 mg/mL in DMSO, <2.3 mg/mL in EtOH, <2.61 mg/mL in H2O
Chemical Name(5R,5aR,8aS,9R)-5-hydroxy-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one
SDFDownload SDF
Canonical SMILESCOC1=CC(=CC(=C1OC)OC)C2C3C(COC3=O)C(C4=CC5=C(C=C24)OCO5)O
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

细胞实验 [1-3]:

细胞系

黑色素瘤细胞,肉瘤细胞,P6细胞,OPM-2和RPMI-8226细胞

溶解方法

该化合物在DMSO中的溶解度大于20.7 mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

反应条件

0.025-1 μM,1 h

应用

在培养的黑色素瘤细胞(FM55和SK-MEL-28),肉瘤细胞(RD-ES)和小鼠细胞系P6(过表达IGF-1R)中,AXL1717(0.05-0.5 μM,48小时)以剂量依赖性方式抑制细胞生长,并诱导凋亡。在P6细胞中,AXL1717(0.025-1 μM)有效抑制IGF-1刺激的IGF-1R以及Akt(丝氨酸473)和Erk1/2磷酸化。AXL1717(1 μM)协同增强ABT-737的抗骨髓瘤活性。在OPM-2和RPMI-8226细胞中,AXL1717(125-500 nM)协同增强ABT-737和ABT-199介导的凋亡。AXL1717(1 μM)抑制5T33MM细胞的DNA合成、趋化性和VEGF分泌。

动物实验 [1-3]:

动物模型

人ES-1、BE和PC3异种移植的SCID小鼠,5T33MM小鼠模型

给药剂量

腹腔注射,20 mg/kg/12 h,8-14 d

应用

在异种移植人ES-1、BE和PC3的SCID小鼠中,AXL1717(20 mg/kg/12 h, i.p.)导致完全的肿瘤消退。在5T33MM小鼠模型中,口服给药AXL1717(1.5 mg/kg)引起BM浆细胞增多症和血清M蛋白水平显著降低。腹腔给药ABT-737和AXL1717(20 mg/kg,每天两次)的组合使用显著延长了总生存期。AXL1717可抑制血管生成,延长总生存期。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

References:

[1]. Girnita A, Girnita L, del Prete F, et al. Cyclolignans as inhibitors of the insulin-like growth factor-1 receptor and malignant cell growth[J]. Cancer research, 2004, 64(1): 236-242.

[2]. Bieghs L, Lub S, Fostier K, et al. The IGF-1 receptor inhibitor picropodophyllin potentiates the anti-myeloma activity of a BH3-mimetic[J]. Oncotarget, 2014, 5(22): 11193.

[3]. Menu E, Jernberg-Wiklund H, Stromberg T, et al. Inhibiting the IGF-1 receptor tyrosine kinase with the cyclolignan PPP: an in vitro and in vivo study in the 5T33MM mouse model[J]. Blood, 2006, 107(2): 655-660.

生物活性

Description AXL1717(苦鬼臼毒素)是一种口服有效的胰岛素样生长因子-1受体(IGF-1R)抑制剂, IC 50值为1 nM。
靶点 IGF1R          
IC50 1 nM          

质量控制