苦鬼臼毒素作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetPicropodophyllinCat. No.: HY-15494CAS No.: 477-47-4分式: CHO分量: 414.41作靶點(diǎn): IGF-1R; Apoptosis作通路: Protein Tyrosine Kinase/RTK; Apoptosis儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 50 mg/mL (120.65 mM; Need ultrasonic)SolventMass1 mg 5 mg 10 m

2、gConcentration制備儲備液1 mM 2.4131 mL 12.0653 mL 24.1307 mL5 mM 0.4826 mL 2.4131 mL 4.8261 mL10 mM 0.2413 mL 1.2065 mL 2.4131 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲存時(shí)，請?jiān)?6 個(gè)內(nèi)使，-20C 儲存時(shí)，請?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn) 請根據(jù)您的實(shí)驗(yàn)動物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都請先按?In Vitr

3、o 式配制澄清的儲備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天 使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可 以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (6.03 mM); Clear solution此案可獲得 2.5 mg/mL (6.03 mM，飽和度未知) 的澄 溶液，此案不適于實(shí)驗(yàn)周 期在半個(gè)以上的實(shí)驗(yàn)。以 1 mL 作液為例，取 100 L 25.0 mg

4、/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITYPage 1 of 2 www.MedChemE物活性 Picropodophyllin (AXL1717)選擇性的胰島素樣長因-1受體 (IGF-1R)抑制劑，IC50 為1 nM。IC & Target IC50: 1 nM (IGF-1R)體外研究 Picropodophyllin (AXL1717) (0.5, 2.5, 10 M) potently inhibits IGF-1-stimulated IGF-1R, Akt (Ser 473) and Erk1/2phosphoryl

5、ation in intact cells. Picropodophyllin (AXL1717) also inhibits cell growth, and induces apoptosis incultured IGF-1R-positive tumor cells1. Picropodophyllin (AXL1717) synergistically sensitizes HMCL, primary humanMM and murine 5T33MM cells to ABT-737 and ABT-199 via further decreasing cell viability

6、 and enhancingapoptosis3. Picropodophyllin and sorafenib synergistically suppress the proliferation and motility of hepatocellularcarcinoma cells4.體內(nèi)研究 Picropodophyllin (AXL1717) (20 mg/kg/12 h, i.p.) causes complete tumor regression in SCID mice xenografted withhuman ES-1, BE, and PC31. Picropodoph

7、yllin (AXL1717) shows a potent antitumor activity, increases survival in the5T33MM mouse model2.PROTOCOLAnimal Four to 5-week-old pathogen-free SCID mice are used and housed within plastic isolators in a sterile facility. ES-1, BE,Administration 1 and PC3 cells (all proved to express IGF-1R), or R-v

8、-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 areinjected with 107JC murine breast cancer cells per mouse in 0.15 mL volume of sterile saline solution. Experimentaltreatm

9、ents with Picropodophyllin (AXL1717) (20 mg/kg/12 h) are performed by daily i.p. injections of the compoundin 10 L volume of DMSO: vegetable oil, 10:1 (v/v). Control mice are treated with the vehicle only. Three animals aretreated in each group. Tumor growth is measured every second day using vernie

10、r calipers, and the tumor volumesare calculated. The mice are carefully observed for the presence of side effects and are sacrificed at the end of theexperiments for histological analysis of the lesions. A separate experiment on Picropodophyllin (AXL1717)-treated(systemically and locally) tumor-free

11、 mice, including histological analyses of various organs, confirms previousobservations that Picropodophyllin (AXL1717) appears to be nontoxic.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Science. 2017 Dec 1;358(6367). pii: eaan4368. EMBO

12、 J. 2019 Aug 1;38(15):e101964. Transl Neurodegener. 2019 Mar 5;8:8. Cancer Sci. 2018 Apr;109(4):1166-1176. Acta Pharmacol Sin. 2016 Feb;37(2):217-27.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Girnita A, et al. Cyclolignans as inhibitors of the insulin-like growt

13、h 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.Page 2 of 3 www.MedC

14、hemE3. Bieghs L, et al. The IGF-1 receptor inhibitor picropodophyllin potentiates the anti-myeloma activity of a BH3-mimetic. Oncotarget. 2014 Nov30;5(22):11193-208.4. Tomizawa M, et al. Picropodophyllin and sorafenib synergistically suppress the proliferation and motility of hepatocellular carcinom

15、a 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 multiplemyeloma 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. 2016Feb;37(