Picropodophyllin (AXL1717) is a selective insulin-like growth factor-1 receptor (IGF-1R) inhibitor with an IC₅₀ of 1 nM.

IC50: 1 nM (IGF-1R)

Picropodophyllin (AXL1717) (0.5, 2.5, 10 μM) potently inhibits IGF-1-stimulated IGF-1R, Akt (Ser 473) and Erk1/2 phosphorylation in intact cells. Picropodophyllin (AXL1717) also inhibits cell growth, and induces apoptosis in cultured IGF-1R-positive tumor cells^[1]. Picropodophyllin (AXL1717) synergistically sensitizes HMCL, primary human MM and murine 5T33MM cells to ABT-737 and ABT-199 via further decreasing cell viability and enhancing apoptosis^[3]. Picropodophyllin and sorafenib synergistically suppress the proliferation and motility of hepatocellular carcinoma cells^[4].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Picropodophyllin (AXL1717) (20 mg/kg/12 h, i.p.) causes complete tumor regression in SCID mice xenografted with human ES-1, BE, and PC3^[1]. Picropodophyllin (AXL1717) shows a potent antitumor activity, increases survival in the 5T33MM mouse model^[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

414.41

C₂₂H₂₂O₈

477-47-4

苦鬼臼毒素

Room temperature in continental US; may vary elsewhere.

DMSO : 50 mg/mL (120.65 mM; Need ultrasonic)

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, 6 months; -20°C, 1 month。-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。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.5 mg/mL (6.03 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.03 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Girnita A, et al. Cyclolignans as inhibitors of the insulin-like growth factor-1 receptor and malignant cell growth. Cancer Res. 2004 Jan 1;64(1):236-42.

  [2]. Menu E, 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. Blood. 2006 Jan 15;107(2):655-60. Epub 2005 Jul 26.

  [3]. Bieghs L, et al. The IGF-1 receptor inhibitor picropodophyllin potentiates the anti-myeloma activity of a BH3-mimetic. Oncotarget. 2014 Nov 30;5(22):11193-208.

  [4]. Tomizawa M, et al. Picropodophyllin and sorafenib synergistically suppress the proliferation and motility of hepatocellular carcinoma cells. Oncol Lett. 2014 Nov;8(5):2023-2026. Epub 2014 Aug 27.

  [5]. Stromberg T, et al. IGF-1 receptor tyrosine kinase inhibition by the cyclolignan PPP induces G2/M-phase accumulation and apoptosis in multiple myeloma cells. Blood. 2006 Jan 15;107(2):669-78. Epub 2005 Sep 15.

  [6]. Kong YL, et al. Insulin deficiency induces rat renal mesangial cell dysfunction via activation of IGF-1/IGF-1R pathway. Acta Pharmacol Sin. 2016 Feb;37(2):217-27.

Four to 5-week-old pathogen-free SCID mice are used and housed within plastic isolators in a sterile facility. ES-1, BE, and PC3 cells (all proved to express IGF-1R), or R-v-src (IGF-1R negative) and P12 (overexpressing IGF-1 and IGF-1R), are injected s.c. at 10⁷ cells/mice in a 0.2 mL volume of sterile saline solution. Immunocompetent Balb-c mice are injected with 107JC murine breast cancer cells per mouse in 0.15 mL volume of sterile saline solution. Experimental treatments with Picropodophyllin (AXL1717) (20 mg/kg/12 h) are performed by daily i.p. injections of the compound in 10 μL volume of DMSO: vegetable oil, 10:1 (v/v). Control mice are treated with the vehicle only. Three animals are treated in each group. Tumor growth is measured every second day using vernier calipers, and the tumor volumes are calculated. The mice are carefully observed for the presence of side effects and are sacrificed at the end of the experiments for histological analysis of the lesions. A separate experiment on Picropodophyllin (AXL1717)-treated (systemically and locally) tumor-free mice, including histological analyses of various organs, confirms previous observations that Picropodophyllin (AXL1717) appears to be nontoxic.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Girnita A, et al. Cyclolignans as inhibitors of the insulin-like growth factor-1 receptor and malignant cell growth. Cancer Res. 2004 Jan 1;64(1):236-42.

  [2]. Menu E, 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. Blood. 2006 Jan 15;107(2):655-60. Epub 2005 Jul 26.

  [3]. Bieghs L, et al. The IGF-1 receptor inhibitor picropodophyllin potentiates the anti-myeloma activity of a BH3-mimetic. Oncotarget. 2014 Nov 30;5(22):11193-208.

  [4]. Tomizawa M, et al. Picropodophyllin and sorafenib synergistically suppress the proliferation and motility of hepatocellular carcinoma cells. Oncol Lett. 2014 Nov;8(5):2023-2026. Epub 2014 Aug 27.

  [5]. Stromberg T, et al. IGF-1 receptor tyrosine kinase inhibition by the cyclolignan PPP induces G2/M-phase accumulation and apoptosis in multiple myeloma cells. Blood. 2006 Jan 15;107(2):669-78. Epub 2005 Sep 15.

  [6]. Kong YL, et al. Insulin deficiency induces rat renal mesangial cell dysfunction via activation of IGF-1/IGF-1R pathway. Acta Pharmacol Sin. 2016 Feb;37(2):217-27.