AXL1717 (Synonyms: AXL 1717, NSC 36407, Picropodophyllin, PPP)

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 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.