AXL1717 (Synonyms: AXL 1717, NSC 36407, Picropodophyllin, PPP) |
| Catalog No.GC17045 |
A potent and selective inhibitor of IGF-1R
Products are for research use only. Not for human use. We do not sell to patients.
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 | |
| Synonyms | AXL 1717, NSC 36407, Picropodophyllin, PPP | ||
| 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 | ||
| Canonical SMILES | COC1=CC(=CC(=C1OC)OC)C2C3C(COC3=O)C(C4=CC5=C(C=C24)OCO5)O | ||
| Formula | C22H22O8 | M.Wt | 414.41 |
| Solubility | ≥ 20.7 mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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