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AXL1717 IGF-1R inhibitor,orally active

Catalog No.A3209
Size Price Stock Qty
10mM (in 1mL DMSO)
$95.00
In stock
10mg
$87.00
In stock
50mg
$308.00
In stock
250mg
$1,337.00
In stock

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Sample solution is provided at 25 µL, 10mM.

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Chemical structure

AXL1717

Biological Activity

Description AXL1717 (Picropodophyllotoxin) is an orally active inhibitor of insulin-like growth factor-1 receptor (IGF-1R) with an IC50 value of 1 nM.
Targets IGF1R          
IC50 1 nM          

Protocol

Cell experiment [1-3]:

Cell lines

Melanoma cells, sarcoma cells, P6 cells, OPM-2 and RPMI-8226 cells

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.

Reacting condition

0.025-1 μM, 1 h

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]:

Animal models

SCID mice xenografted with human ES-1, BE, and PC3; 5T33MM murine model;

Dosage form

Intraperitoneal injection, 20 mg/kg/12 h, 8–14 days

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.

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.

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.

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Chemical Properties

Cas No. 477-47-4 SDF Download SDF
Synonyms Picropodophyllotoxin;Picropodophyllin;PPP;AXL-1717;AXL 1717
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 >20.7mg/mL in DMSO Storage Store at -20°C
Shipping Condition Evaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.

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.