AXL1717
(Synonyms: 苦鬼臼毒素; AXL1717; Picropodophyllin; PPP) 目录号 : GC17045
A potent and selective inhibitor of IGF-1R
Cas No.:477-47-4
Sample solution is provided at 25 µL, 10mM.
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.
| Cell experiment [1-3]: | |
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Cell lines |
Melanoma cells, sarcoma cells, P6 cells, OPM-2 and RPMI-8226 cells |
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Preparation method |
The solubility of this compound in DMSO > 20.7 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
0.025-1 μM, 1 h |
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Applications |
AXL1717 (0.05-0.5 μM, 48 h) dose-dependently inhibited cell growth, and induced apoptosis in cultured melanoma cells (FM 55 and SK-MEL-28), sarcoma cells (RD-ES), and the mouse cell line P6 (overexpressing IGF-1R). In P6 cells, AXL1717 (0.025-1 μM) efficiently inhibited IGF-1-stimulated IGF-1R, as well as Akt (serine 473) and Erk1/2 phosphorylation. AXL1717 (1 μM) synergistically enhanced the anti-myeloma activity of ABT-737. In OPM-2 and RPMI-8226 cells, AXL1717 (125-500 nM) synergistically enhanced ABT-737 and ABT-199 mediated apoptosis. AXL1717 (1 μM) inhibited DNA synthesis, chemotaxis, and VEGF secretion of 5T33MM cells. |
| Animal experiment [1-3]: | |
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Animal models |
SCID mice xenografted with human ES-1, BE, and PC3; 5T33MM murine model; |
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Dosage form |
Intraperitoneal injection, 20 mg/kg/12 h, 8–14 days |
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Application |
In SCID mice xenografted with human ES-1, BE, and PC3, AXL1717 (20 mg/kg/12 h, i.p.) resulted in complete tumor regression. In 5T33MM murine model, AXL1717 (1.5 mg/kg, oral administration) showed a strong and significant reduction in BM plasmacytosis and serum M-protein levels. The combination of ABT-737 and AXL1717 (20 mg/kg, twice a day, intraperitoneally) did significantly and strongly prolong the overall survival. AXL1717 inhibited angiogenesis and prolonged the overall survival. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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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. | |
| Cas No. | 477-47-4 | SDF | |
| 别名 | 苦鬼臼毒素; AXL1717; Picropodophyllin; PPP | ||
| 化学名 | (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 | ||
| Canonical SMILES | COC1=CC(=CC(=C1OC)OC)C2C3C(COC3=O)C(C4=CC5=C(C=C24)OCO5)O | ||
| 分子式 | C22H22O8 | 分子量 | 414.41 |
| 溶解度 | ≥ 20.7 mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4131 mL | 12.0653 mL | 24.1307 mL |
| 5 mM | 0.4826 mL | 2.4131 mL | 4.8261 mL |
| 10 mM | 0.2413 mL | 1.2065 mL | 2.4131 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet