Coramsine

Coramsine

Coramsine or Coramsine/SBP002 is a chemotherapeutic and immunomodulating agent whose primary ingredients are two solasodine glycoalkaloids, solasonine and solamargine, derived from Solanum linnaeanum (Devil's Apple).

The use of glycoalkaloids as anti-cancer agents was discovered by Queensland researcher Dr. Bill Cham in the late 1970s after hearing reports from farmers that topical application of the Devil's Apple plant was effective in slowing the growth of various skin cancers on horses and cattle.

Animal studies[1][2] and in vitro human trials[3] showed positive results, however Cham decided to focus his energies on developing the glycoalkaloid mixture, patented as BEC, as a topical cream for non-melanoma skin cancer.[4][5][6]

In 2000 Solbec Pharmaceuticals Ltd. licensed BEC's intellectual property rights from Dr. Cham and after displaying good results against peritoneal mesothelioma in animals Solbec initiated human trials which also yielded encouraging results.[7][8] Other researchers have also demonstrated antiproliferative activity of steroidal glycosides against cancer cells.[9][10]

During 2005 and 2006 Solbec was granted orphan drug designation for Coramsine by the U.S. Food and Drug Administration in the treatment of renal cell carcinoma and for malignant melanoma respectively.[11] 2006 also saw the completion of Phase I/IIa trials and the commissioning of Phase IIb trials that would target renal cell carcinoma (stage III/IV) and malignant melanoma (stage III/IV), but in November 2006 shortly before their commencement Solbec postponed the trials due to Australia's Therapeutic Goods Administration (TGA) having concerns about the drug's pre-clinical data. A development plan for Coramsine was approved by the TGA in May 2007 resulting in further pre-clinical studies, which were successfully completed in March 2008. Solbec unsuccessfully sought a business partner to develop Corasmine further but changed business name and direction in December 2008 and subsequent company licensed the technology back to the original founder.[12]

Cormasine is thought to kill tumor cells by direct cell lysis, showing selectivity for cancer cells as opposed to healthy cells via a patented rhamnose binding protein.[13][14] Coramsine also has the potential to modulate the production of Interleukin-6.[15]

References

  1. ^ Cham BE, Gilliver M, Wilson L (1987). "Antitumour effects of glycoalkaloids isolated from Solanum sodomaeum". Planta Med 53 (1): 34–6. doi:10.1055/s-2006-962612. PMID 3575510. 
  2. ^ Cham BE, Daunter B (1990). "Solasodine glycosides. Selective cytotoxicity for cancer cells and inhibition of cytotoxicity by rhamnose in mice with sarcoma 180.". Cancer Lett 55 (3): 221–5. doi:10.1016/0304-3835(90)90122-E. PMID 2257540. 
  3. ^ Cham BE, Daunter B (1990). "Solasodine glycosides. In vitro preferential cytotoxicity for human cancer cells". Cancer Letters 55 (3): 209–20. doi:10.1016/0304-3835(90)90121-D. PMID 2257539. 
  4. ^ Cham BE, Daunter B, Evans RA (1991). "Topical treatment of malignant and premalignant skin lesions by very low concentrations of a standard mixture (BEC) of solasodine glycosides.". Cancer Lett. 59 (3): 183–92. doi:10.1016/0304-3835(91)90140-D. PMID 1913614. 
  5. ^ Punjabi S, Cook LJ, Kersey P, Marks R, Cerio R (2008). "Solasodine glycoalkaloids: a novel topical therapy for basal cell carcinoma. A double-blind, randomized, placebo-controlled, parallel group, multicenter study.". Int J Dermatol. 47 (1): 78–82. doi:10.1111/j.1365-4632.2007.03363.x. PMID 18173610. http://www3.interscience.wiley.com/cgi-bin/fulltext/119389345/PDFSTART. 
  6. ^ "http://www.solbec.com.au/investorasx.asp?CATEGORY=3".Solbec Pharmaceuticals. Retrieved on 15 October 2008.
  7. ^ Amalfi, Carmelo (2006-07-06). "The little mouse who wouldn’t say die". Cosmos Magazine. http://www.cosmosmagazine.com/node/471. Retrieved 2008-10-15. 
  8. ^ Millward M, Powell A, Tyson S, Daly P, Ferguson R, Carter S (2005). "Phase I trial of coramsine SBP002 in patients with advanced solid tumors. Abstract of presentation at 2005 ASCO Annual Meeting.". J. Clin. Oncol. 23 (16_suppl): 3105. http://meeting.jco.org/cgi/content/abstract/23/16_suppl/3105. Retrieved 2008-10-15. 
  9. ^ Ono M, Nishimura K, Suzuki K, Fukushima T, Igoshi K, Yoshimitsu H, Ikeda T, Nohara T (2006). "Steroidal glycosides from the underground parts of Solanum sodomaeum.". Chem Pharm Bull 54 (2): 230–3. doi:10.1248/cpb.54.230. PMID 16462070. 
  10. ^ Lee KR, Kozukue N, Han JS, Park JH, Chang EY, Baek EJ, Chang JS, Friedman M (2004). "Glycoalkaloids and metabolites inhibit the growth of human colon (HT29) and liver (HepG2) cancer cells". J Agric Food Chem 52 (10): 2832–9. doi:10.1021/jf030526d. PMID 15137822. 
  11. ^ "http://www.fda.gov/orphan/designat/list.xls". U.S. Food and Drug Administration. Retrieved on 15 October 2008.
  12. ^ "coramsinetechnologylicence2104|09.pdf". http://www.freedomeye.com.au/index.php?option=com_phocadownload&view=category&id=1:updates&Itemid=74. 
  13. ^ van der Most RG, Himbeck R, Aarons S, Carter SJ, Larma I, Robinson C, Currie A, Lake RA. (2006). "Antitumor efficacy of the novel chemotherapeutic agent coramsine is potentiated by cotreatment with CpG-containing oligodeoxynucleotides". J Immunother. 29 (2): 134–42. doi:10.1097/01.cji.0000187958.38179.a9. PMID 16531814. 
  14. ^ Rhamnose binding protein. 2008 (published 2008-03-23). 
  15. ^ "Coramsine - Other Applications". http://solbec.com.au/general.asp?PAGE_ID=41. Retrieved 2008-10-31. 

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