Picropodophyllin
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MedKoo CAT#: 205812

CAS#: 477-47-4

Description: Picropodophyllin, also known as Picropodophyllotoxin, AXL1717 or PPP, is a cyclolignan alkaloid found in the mayapple plant family (Podophyllum peltatum), and a small molecule inhibitor of the insulin-like growth factor 1 receptor (IGF1R) with potential antineoplastic activity. Picropodophyllin specifically inhibits the activity and downregulates the cellular expression of IGF1R without interfering with activities of other growth factor receptors, such as receptors for insulin, epidermal growth factor, platelet-derived growth factor, fibroblast growth factor and mast/stem cell growth factor (KIT). This agent shows potent activity in the suppression o f tumor cell proliferation and the induction of tumor cell apoptosis.


Chemical Structure

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Picropodophyllin
CAS# 477-47-4

Theoretical Analysis

MedKoo Cat#: 205812
Name: Picropodophyllin
CAS#: 477-47-4
Chemical Formula: C22H22O8
Exact Mass: 414.13147
Molecular Weight: 414.40528
Elemental Analysis: C, 63.76; H, 5.35; O, 30.89

Price and Availability

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10.0mg USD 150.0 Same day
25.0mg USD 250.0 Same day
50.0mg USD 450.0 Same day
100.0mg USD 750.0 Same day
200.0mg USD 1250.0 Same day
500.0mg USD 1950.0 Same day
1.0g USD 2950.0 Same day
2.0g USD 5250.0 Same day
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Synonym: AXL1717; AXL-1717; AXL 1717; PPP; picropodophyllin; Picropodophyllotoxin.

IUPAC/Chemical Name: (5R,5aS,8aR,9R)-9-hydroxy-5-(3,4,5-trimethoxyphenyl)-5,5a,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(8H)-one

InChi Key: YJGVMLPVUAXIQN-HAEOHBJNSA-N

InChi Code: InChI=1S/C22H22O8/c1-25-16-4-10(5-17(26-2)21(16)27-3)18-11-6-14-15(30-9-29-14)7-12(11)20(23)13-8-28-22(24)19(13)18/h4-7,13,18-20,23H,8-9H2,1-3H3/t13-,18+,19+,20-/m0/s1

SMILES Code: O=C1OC[C@]2([H])[C@@H](O)C3=C(C=C4OCOC4=C3)[C@@H](C5=CC(OC)=C(OC)C(OC)=C5)[C@@]21[H]

Appearance: white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Preparing Stock Solutions

The following data is based on the product molecular weight 414.40528 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL

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1: E C, Li J, Shao D, Zhang D, Pan Y, Chen L, Zhang X. The insulin-like growth factor-I receptor inhibitor picropodophyllin-induced selective apoptosis of hepatocellular carcinoma cell through a caspase-dependent mitochondrial pathway. Oncol Res. 2014;21(2):103-10. doi: 10.3727/096504013X13808175127324. PubMed PMID: 24406046.

2: Huang Z, Fang Z, Zhen H, Zhou L, Amin HM, Shi P. Inhibition of type I insulin-like growth factor receptor tyrosine kinase by picropodophyllin induces apoptosis and cell cycle arrest in T lymphoblastic leukemia/lymphoma. Leuk Lymphoma. 2014 Feb 17. [Epub ahead of print] PubMed PMID: 24206093.

3: Wang Q, Wei F, Lv G, Li C, Liu T, Hadjipanayis CG, Zhang G, Hao C, Bellail AC. The association of TP53 mutations with the resistance of colorectal carcinoma to the insulin-like growth factor-1 receptor inhibitor picropodophyllin. BMC Cancer. 2013 Nov 4;13:521. doi: 10.1186/1471-2407-13-521. PubMed PMID: 24182354; PubMed Central PMCID: PMC3840673.

4: Yin SC, Guo W, Tao ZZ. Picropodophyllin inhibits tumor growth of human nasopharyngeal carcinoma in a mouse model. Biochem Biophys Res Commun. 2013 Sep 13;439(1):1-5. doi: 10.1016/j.bbrc.2013.08.050. Epub 2013 Aug 22. PubMed PMID: 23973483.

5: Wu X, Sooman L, Wickström M, Fryknäs M, Dyrager C, Lennartsson J, Gullbo J. Alternative cytotoxic effects of the postulated IGF-IR inhibitor picropodophyllin in vitro. Mol Cancer Ther. 2013 Aug;12(8):1526-36. doi: 10.1158/1535-7163.MCT-13-0091. Epub 2013 May 22. PubMed PMID: 23699657.

6: Lu X, Wang L, Mei J, Wang X, Zhu X, Zhang Q, Lv J. Picropodophyllin inhibits epithelial ovarian cancer cells in vitro and in vivo. Biochem Biophys Res Commun. 2013 Jun 7;435(3):385-90. doi: 10.1016/j.bbrc.2013.04.097. Epub 2013 May 9. PubMed PMID: 23665331.

7: Lemaire M, Fristedt C, Agarwal P, Menu E, Van Valckenborgh E, De Bruyne E, Österborg A, Atadja P, Larsson O, Axelson M, Van Camp B, Jernberg-Wiklund H, Vanderkerken K. The HDAC inhibitor LBH589 enhances the antimyeloma effects of the IGF-1RTK inhibitor picropodophyllin. Clin Cancer Res. 2012 Apr 15;18(8):2230-9. doi: 10.1158/1078-0432.CCR-11-1764. Epub 2012 Mar 5. PubMed PMID: 22392915.

8: Feng X, Aleem E, Lin Y, Axelson M, Larsson O, Strömberg T. Multiple antitumor effects of picropodophyllin in colon carcinoma cell lines: clinical implications. Int J Oncol. 2012 Apr;40(4):1251-8. doi: 10.3892/ijo.2011.1281. Epub 2011 Dec 6. PubMed PMID: 22159423; PubMed Central PMCID: PMC3584617.

9: Doghman M, Axelson M, Lalli E. Potent inhibitory effect of the cyclolignan picropodophyllin (PPP) on human adrenocortical carcinoma cells proliferation. Am J Cancer Res. 2011;1(3):356-361. Epub 2011 Jan 5. PubMed PMID: 21968616; PubMed Central PMCID: PMC3180063.

10: Hashemi J, Worrall C, Vasilcanu D, Fryknäs M, Sulaiman L, Karimi M, Weng WH, Lui WO, Rudduck C, Axelson M, Jernberg-Wiklund H, Girnita L, Larsson O, Larsson C. Molecular characterization of acquired tolerance of tumor cells to picropodophyllin (PPP). PLoS One. 2011 Mar 14;6(3):e14757. doi: 10.1371/journal.pone.0014757. PubMed PMID: 21423728; PubMed Central PMCID: PMC3056661.

11: Rönquist-Nii Y, Eksborg S, Axelson M, Harmenberg J, Ekman S, Bergqvist M, Beck O. Determination of picropodophyllin and its isomer podophyllotoxin in human serum samples with electrospray ionization of hexylamine adducts by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Feb 15;879(5-6):326-34. doi: 10.1016/j.jchromb.2010.12.017. Epub 2010 Dec 28. Erratum in: J Chromatogr B Analyt Technol Biomed Life Sci. 2012 Mar 15;889-890:148. Ekman, Simon [added]; Bergqvist, Michael [added]. PubMed PMID: 21251888.

12: Ohshima-Hosoyama S, Hosoyama T, Nelon LD, Keller C. IGF-1 receptor inhibition by picropodophyllin in medulloblastoma. Biochem Biophys Res Commun. 2010 Sep 3;399(4):727-32. doi: 10.1016/j.bbrc.2010.08.009. Epub 2010 Aug 6. PubMed PMID: 20692232.

13: Yin S, Girnita A, Strömberg T, Khan Z, Andersson S, Zheng H, Ericsson C, Axelson M, Nistér M, Larsson O, Ekström TJ, Girnita L. Targeting the insulin-like growth factor-1 receptor by picropodophyllin as a treatment option for glioblastoma. Neuro Oncol. 2010 Jan;12(1):19-27. doi: 10.1093/neuonc/nop008. Epub 2009 Oct 20. PubMed PMID: 20150364; PubMed Central PMCID: PMC2940558.

14: Duan Z, Choy E, Harmon D, Yang C, Ryu K, Schwab J, Mankin H, Hornicek FJ. Insulin-like growth factor-I receptor tyrosine kinase inhibitor cyclolignan picropodophyllin inhibits proliferation and induces apoptosis in multidrug resistant osteosarcoma cell lines. Mol Cancer Ther. 2009 Aug;8(8):2122-30. doi: 10.1158/1535-7163.MCT-09-0115. Epub 2009 Jul 28. PubMed PMID: 19638450; PubMed Central PMCID: PMC2766237.

15: Economou MA, Wu J, Vasilcanu D, Rosengren L, All-Ericsson C, van der Ploeg I, Menu E, Girnita L, Axelson M, Larsson O, Seregard S, Kvanta A. Inhibition of VEGF secretion and experimental choroidal neovascularization by picropodophyllin (PPP), an inhibitor of the insulin-like growth factor-1 receptor. Acta Ophthalmol. 2008 Nov;86 Thesis 4:42-9. doi: 10.1111/j.1755-3768.2008.01185.x. PubMed PMID: 19032681.

16: Economou MA, Andersson S, Vasilcanu D, All-Ericsson C, Menu E, Girnita A, Girnita L, Axelson M, Seregard S, Larsson O. Oral picropodophyllin (PPP) is well tolerated in vivo and inhibits IGF-1R expression and growth of uveal melanoma. Acta Ophthalmol. 2008 Nov;86 Thesis 4:35-41. doi: 10.1111/j.1755-3768.2008.01184.x. PubMed PMID: 19032680.

17: Girnita A, All-Ericsson C, Economou MA, Aström K, Axelson M, Seregard S, Larsson O, Girnita L. The insulin-like growth factor-I receptor inhibitor picropodophyllin causes tumor regression and attenuates mechanisms involved in invasion of uveal melanoma cells. Acta Ophthalmol. 2008 Nov;86 Thesis 4:26-34. doi: 10.1111/j.1755-3768.2008.01183.x. PubMed PMID: 19032679.

18: Tomizawa M, Yokosuka O. Picropodophyllin suppresses the proliferation and invasion of hepatocellular carcinoma under serum starvation. Mol Med Rep. 2008 Sep-Oct;1(5):685-8. doi: 10.3892/mmr_00000013. PubMed PMID: 21479470.

19: Vitale M, Prestat G, Lopes D, Madec D, Kammerer C, Poli G, Girnita L. New picropodophyllin analogs via palladium-catalyzed allylic alkylation-Hiyama cross-coupling sequences. J Org Chem. 2008 Aug 1;73(15):5795-805. doi: 10.1021/jo800707q. Epub 2008 Jun 25. PubMed PMID: 18576606.

20: Economou MA, Wu J, Vasilcanu D, Rosengren L, All-Ericsson C, van der Ploeg I, Menu E, Girnita L, Axelson M, Larsson O, Seregard S, Kvanta A. Inhibition of VEGF secretion and experimental choroidal neovascularization by picropodophyllin (PPP), an inhibitor of the insulin-like growth factor-1 receptor. Invest Ophthalmol Vis Sci. 2008 Jun;49(6):2620-6. doi: 10.1167/iovs.07-0742. PubMed PMID: 18515591.



Additional Information

AXL1717 is the first targeted oral small-molecule IGF-1 receptor inhibitor with no effect on the insulin receptor. AXL1717 is presently undergoing phase I/II clinical trials and the compound combines a superior preclinical efficacy against numerous tumors with an excellent tolerability profile. Most tumor cells are dependent on the IGF-1 receptor signal pathway and the IGF-1 receptor is therefore regarded as a very promising target for cancer therapy. To date, there are no IGF-1 receptor inhibitor drugs on the market.   AXL1717 is currently being developed by Axelar (source: http://www.axelar.se/pipeline.html).
 
AXL1717 demonstrates strong anti-tumor efficacy, including tumor extermination, in animals xenografted with human malignant cells, including breast cancer, prostate cancer, glioblastoma (intracerebral implants), malignant melanoma, sarcoma and multiple myeloma. Axelar has successfully completed its first Phase I/II clinical study in 49 advanced-stage cancer patients with solid tumors. The study reached all objectives with respect to safety, bioavailability and the recommended phase II dose was identified. Even though the study was not primarily designed for efficacy assessments, signs suggesting treatment benefit were reported.