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Squalamine

Squalamine is an essential ingredient which may be derived from various sources in nature. One known source of squalamine is predominantly found in the liver tissue (not the "liver oil") of the deep water shark. The "liver oil" of the shark contains only trace amounts of the compound squalamine, however, it also contains many other exotic compounds.  Squalamine is not a protein. Instead, it is the first known example of a class of compounds called aminosterols, each being a steroid chemically linked to an amino acid. Proteins are easily destroyed by digestive enzymes in the stomach, however, squalamine remains unscathed through the digestive tract. 

Angiogenesis is a function in the body where unhealthy cells develop their own blood vessel structure in order to nourish and support themselves. The immune system, in response, uses certain compounds in the body to naturally counter angiogenesis. This normal body function is called anti-angiogenesis.  If the immune system is successful in carrying out this designed natural function, unhealthy cells can not survive. However, if the body is deficient in these vital compounds, anti-angiogenesis can not occur. Therefore, it is important to supplement the body with natural anti-angiogenesis factors. Squalamine is an aminosterol compound which the body readily uses to carry out its normal anti-angiogenesis function. see http://www.squalamine.com/.

Current developer:   

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2: Lavigne JP, Brunel JM, Chevalier J, Pagès JM. Squalamine, an original chemosensitizer to combat antibiotic-resistant gram-negative bacteria. J Antimicrob Chemother. 2010 Apr;65(4):799-801. Epub 2010 Feb 10. PubMed PMID: 20147322.

3: Di Pasquale E, Salmi-Smail C, Brunel JM, Sanchez P, Fantini J, Maresca M. Biophysical studies of the interaction of squalamine and other cationic amphiphilic molecules with bacterial and eukaryotic membranes: importance of the distribution coefficient in membrane selectivity. Chem Phys Lipids. 2010 Feb;163(2):131-40. Epub 2009 Oct 31. PubMed PMID: 19883637.

4: Alhanout K, Brunel JM, Raoult D, Rolain JM. In vitro antibacterial activity of aminosterols against multidrug-resistant bacteria from patients with cystic fibrosis. J Antimicrob Chemother. 2009 Oct;64(4):810-4. Epub 2009 Aug 7. PubMed PMID: 19666647.

5: Salmi C, Loncle C, Vidal N, Laget M, Letourneux Y, Brunel JM. Antimicrobial activities of 3-amino- and polyaminosterol analogues of squalamine and trodusquemine. J Enzyme Inhib Med Chem. 2008 Dec;23(6):860-5. PubMed PMID: 19005944.

6: Singh R, Sharma M, Joshi P, Rawat DS. Clinical status of anti-cancer agents derived from marine sources. Anticancer Agents Med Chem. 2008 Aug;8(6):603-17. Review. PubMed PMID: 18690825.

7: Salmi C, Loncle C, Vidal N, Letourneux Y, Fantini J, Maresca M, Taïeb N, Pagès JM, Brunel JM. Squalamine: an appropriate strategy against the emergence of multidrug resistant gram-negative bacteria? PLoS One. 2008 Jul 23;3(7):e2765. PubMed PMID: 18648511; PubMed Central PMCID: PMC2447875.

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13: Salmi C, Loncle C, Vidal N, Letourneux Y, Brunel JM. New stereoselective titanium reductive amination synthesis of 3-amino and polyaminosterol derivatives possessing antimicrobial activities. Eur J Med Chem. 2008 Mar;43(3):540-7. Epub 2007 May 5. PubMed PMID: 17566609.

14: Chen WH, Shao XB, Moellering R, Wennersten C, Regen SL. A bioconjugate approach toward squalamine mimics: Insight into the mechanism of biological action. Bioconjug Chem. 2006 Nov-Dec;17(6):1582-91. PubMed PMID: 17105239.

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21: Brunel JM, Salmi C, Loncle C, Vidal N, Letourneux Y. Squalamine: a polyvalent drug of the future? Curr Cancer Drug Targets. 2005 Jun;5(4):267-72. Review. PubMed PMID: 15975047.

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26: Choucair B, Dherbomez M, Roussakis C, El-kihel L. Synthesis of 7 alpha- and 7 beta-spermidinylcholesterol, squalamine analogues. Bioorg Med Chem Lett. 2004 Aug 16;14(16):4213-6. PubMed PMID: 15261272.

27: Higgins RD, Yan Y, Geng Y, Zasloff M, Williams JI. Regression of retinopathy by squalamine in a mouse model. Pediatr Res. 2004 Jul;56(1):144-9. Epub 2004 May 5. PubMed PMID: 15128931.

28: Li AC, Sabo AM, McCormick T, Johnston SM. Quantitative analysis of squalamine, a self-ionization-suppressing aminosterol sulfate, in human plasma by LC-MS/MS. J Pharm Biomed Anal. 2004 Feb 18;34(3):631-41. PubMed PMID: 15127819.

29: Cho J, Kim Y. Sharks: a potential source of antiangiogenic factors and tumor treatments. Mar Biotechnol (NY). 2002 Dec;4(6):521-5. PubMed PMID: 14961226.

30: Ciulla TA, Criswell MH, Danis RP, Williams JI, McLane MP, Holroyd KJ. Squalamine lactate reduces choroidal neovascularization in a laser-injury model in the rat. Retina. 2003 Dec;23(6):808-14. PubMed PMID: 14707832.

31: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2003 Oct;25(8):653-82. PubMed PMID: 14671684.

32: Sridhar SS, Shepherd FA. Targeting angiogenesis: a review of angiogenesis inhibitors in the treatment of lung cancer. Lung Cancer. 2003 Dec;42 Suppl 1:S81-91. Review. PubMed PMID: 14611919.

33: Okumura K, Nakamura Y, Takeuchi S, Kato I, Fujimoto Y, Ikekawa N. Formal synthesis of squalamine from desmosterol. Chem Pharm Bull (Tokyo). 2003 Oct;51(10):1177-82. PubMed PMID: 14519925.

34: Herbst RS, Hammond LA, Carbone DP, Tran HT, Holroyd KJ, Desai A, Williams JI, Bekele BN, Hait H, Allgood V, Solomon S, Schiller JH. A phase I/IIA trial of continuous five-day infusion of squalamine lactate (MSI-1256F) plus carboplatin and paclitaxel in patients with advanced non-small cell lung cancer. Clin Cancer Res. 2003 Sep 15;9(11):4108-15. PubMed PMID: 14519633.

35: Zhang DH, Cai F, Zhou XD, Zhou WS. A concise and stereoselective synthesis of squalamine. Org Lett. 2003 Sep 4;5(18):3257-9. PubMed PMID: 12943401.

36: Shepherd FA, Sridhar SS. Angiogenesis inhibitors under study for the treatment of lung cancer. Lung Cancer. 2003 Aug;41 Suppl 1:S63-72. Review. PubMed PMID: 12867064.

37: Hao D, Hammond LA, Eckhardt SG, Patnaik A, Takimoto CH, Schwartz GH, Goetz AD, Tolcher AW, McCreery HA, Mamun K, Williams JI, Holroyd KJ, Rowinsky EK. A Phase I and pharmacokinetic study of squalamine, an aminosterol angiogenesis inhibitor. Clin Cancer Res. 2003 Jul;9(7):2465-71. PubMed PMID: 12855619.

38: Li CJ, Kari UP, Noecker LA, Jones SR, Sabo AM, McCormick TJ, Johnston SM. Determination of degradation products of squalamine lactate using LC/MS. J Pharm Biomed Anal. 2003 Apr 24;32(1):85-96. PubMed PMID: 12852451.

39: Genaidy M, Kazi AA, Peyman GA, Passos-Machado E, Farahat HG, Williams JI, Holroyd KJ, Blake DA. Effect of squalamine on iris neovascularization in monkeys. Retina. 2002 Dec;22(6):772-8. PubMed PMID: 12476105.

40: Savage PB, Li C, Taotafa U, Ding B, Guan Q. Antibacterial properties of cationic steroid antibiotics. FEMS Microbiol Lett. 2002 Nov 19;217(1):1-7. Review. PubMed PMID: 12445638.

41: Ahima RS, Patel HR, Takahashi N, Qi Y, Hileman SM, Zasloff MA. Appetite suppression and weight reduction by a centrally active aminosterol. Diabetes. 2002 Jul;51(7):2099-104. PubMed PMID: 12086938.

42: Li D, Williams JI, Pietras RJ. Squalamine and cisplatin block angiogenesis and growth of human ovarian cancer cells with or without HER-2 gene overexpression. Oncogene. 2002 Apr 25;21(18):2805-14. PubMed PMID: 11973639.

43: Shu Y, Jones SR, Kinney WA, Selinsky BS. The synthesis of spermine analogs of the shark aminosterol squalamine. Steroids. 2002 Mar;67(3-4):291-304. PubMed PMID: 11856553.

44: Yin M, Gentili C, Koyama E, Zasloff M, Pacifici M. Antiangiogenic treatment delays chondrocyte maturation and bone formation during limb skeletogenesis. J Bone Miner Res. 2002 Jan;17(1):56-65. PubMed PMID: 11771670.

45: Bhargava P, Marshall JL, Dahut W, Rizvi N, Trocky N, Williams JI, Hait H, Song S, Holroyd KJ, Hawkins MJ. A phase I and pharmacokinetic study of squalamine, a novel antiangiogenic agent, in patients with advanced cancers. Clin Cancer Res. 2001 Dec;7(12):3912-9. PubMed PMID: 11751482.

46: Marwick C. Natural compounds show antiangiogenic activity. J Natl Cancer Inst. 2001 Nov 21;93(22):1685. PubMed PMID: 11717328.

47: Jiang C, Lee ER, Lane MB, Xiao YF, Harris DJ, Cheng SH. Partial correction of defective Cl(-) secretion in cystic fibrosis epithelial cells by an analog of squalamine. Am J Physiol Lung Cell Mol Physiol. 2001 Nov;281(5):L1164-72. PubMed PMID: 11597908.

48: Williams JI, Weitman S, Gonzalez CM, Jundt CH, Marty J, Stringer SD, Holroyd KJ, Mclane MP, Chen Q, Zasloff M, Von Hoff DD. Squalamine treatment of human tumors in nu/nu mice enhances platinum-based chemotherapies. Clin Cancer Res. 2001 Mar;7(3):724-33. PubMed PMID: 11297269.

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51: Kim HS, Choi BS, Kwon KC, Lee SO, Kwak HJ, Lee CH. Synthesis and antimicrobial activity of squalamine analogue. Bioorg Med Chem. 2000 Aug;8(8):2059-65. PubMed PMID: 11003150.

52: Kinney WA, Zhang X, Williams JI, Johnston S, Michalak RS, Deshpande M, Dostal L, Rosazza JP. A short formal synthesis of squalamine from a microbial metabolite. Org Lett. 2000 Sep 21;2(19):2921-2. PubMed PMID: 10986072.

53: Khabnadideh S, Tan CL, Croft SL, Kendrick H, Yardley V, Gilbert IH. Squalamine analogues as potential anti-trypanosomal and anti-leishmanial compounds. Bioorg Med Chem Lett. 2000 Jun 5;10(11):1237-9. PubMed PMID: 10866389.

54: Rao MN, Shinnar AE, Noecker LA, Chao TL, Feibush B, Snyder B, Sharkansky I, Sarkahian A, Zhang X, Jones SR, Kinney WA, Zasloff M. Aminosterols from the dogfish shark Squalus acanthias. J Nat Prod. 2000 May;63(5):631-5. PubMed PMID: 10843574.

55: Higgins RD, Sanders RJ, Yan Y, Zasloff M, Williams JI. Squalamine improves retinal neovascularization. Invest Ophthalmol Vis Sci. 2000 May;41(6):1507-12. PubMed PMID: 10798670.

56: Selinsky BS, Smith R, Frangiosi A, Vonbaur B, Pedersen L. Squalamine is not a proton ionophore. Biochim Biophys Acta. 2000 Mar 15;1464(1):135-41. PubMed PMID: 10704927.

57: Schiller JH, Bittner G. Potentiation of platinum antitumor effects in human lung tumor xenografts by the angiogenesis inhibitor squalamine: effects on tumor neovascularization. Clin Cancer Res. 1999 Dec;5(12):4287-94. PubMed PMID: 10632372.

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59: Alper SL, Chernova MN, Williams J, Zasloff M, Law FY, Knauf PA. Differential inhibition of AE1 and AE2 anion exchangers by oxonol dyes and by novel polyaminosterol analogs of the shark antibiotic squalamine. Biochem Cell Biol. 1998;76(5):799-806. PubMed PMID: 10353714.

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62: Sills AK Jr, Williams JI, Tyler BM, Epstein DS, Sipos EP, Davis JD, McLane MP, Pitchford S, Cheshire K, Gannon FH, Kinney WA, Chao TL, Donowitz M, Laterra J, Zasloff M, Brem H. Squalamine inhibits angiogenesis and solid tumor growth in vivo and perturbs embryonic vasculature. Cancer Res. 1998 Jul 1;58(13):2784-92. PubMed PMID: 9661892.

63: Russo TA, Mylotte D. Expression of the K54 and O4 specific antigen has opposite effects on the bactericidal activity of squalamine against an extraintestinal isolate of Escherichia coli. FEMS Microbiol Lett. 1998 May 15;162(2):311-5. PubMed PMID: 9627966.

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