“Coramsine”的意思、由来-开放百科全书

Coramsine (SBP002) was an experimental cancer drug that was evaluated in preliminary clinical trials, but was abandoned by Solbec Pharmaceuticals Ltd after the results were insufficient for them to raise investment capital to continue its development.

Composition

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

History

The study of glycoalkaloids as potential anti-cancer agents began with Queensland researcher Bill Cham in the late 1970s. Cham heard 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.{{cn|date=November 2018}}

Animal studies^[1]^[2] and in vitro studies^[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 the intellectual property rights to BEC from Cham and after it displayed 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 coramsine further, abandoning its development, as they changed the company's direction as well as its legal business name in December 2008, following the US investment market's late-2008 turmoil and ensuing credit crunch.^[12] The subsequent company licensed the technology back to the original founder, Bill Cham, who manufactures it from his private company in Vanuatu and markets it worldwide via the internet under the name Curaderm BEC5, a cream of solasodine rhamnosyl glycosides (BEC). Curaderm BEC5 has not been approved for medical use by any regulatory agency.

Mechanism of action

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

References

1. ^{{cite journal|vauthors=Cham BE, Gilliver M, Wilson L|title=Antitumour effects of glycoalkaloids isolated from Solanum sodomaeum|journal=Planta Med|year=1987 |volume=53|issue=1|pages=34–6|pmid=3575510|doi=10.1055/s-2006-962612}}
2. ^{{cite journal|vauthors=Cham BE, Daunter B|title=Solasodine glycosides. Selective cytotoxicity for cancer cells and inhibition of cytotoxicity by rhamnose in mice with sarcoma 180.|journal=Cancer Lett|year=1990|volume=55|issue=3|pages=221–5|pmid= 2257540|doi=10.1016/0304-3835(90)90122-E }}
3. ^{{cite journal|vauthors=Cham BE, Daunter B|title=Solasodine glycosides. In vitro preferential cytotoxicity for human cancer cells|journal=Cancer Letters|volume=55|issue=3|pages=209–20|pmid=2257539|doi=10.1016/0304-3835(90)90121-D|year=1990}}
4. ^{{cite journal|vauthors=Cham BE, Daunter B, Evans RA| title=Topical treatment of malignant and premalignant skin lesions by very low concentrations of a standard mixture (BEC) of solasodine glycosides.|journal=Cancer Lett.|year=1991 |volume=59|issue=3|pages=183–92|pmid=1913614|doi=10.1016/0304-3835(91)90140-D}}
5. ^{{cite journal|vauthors=Punjabi S, Cook LJ, Kersey P, Marks R, Cerio R|title=Solasodine glycoalkaloids: a novel topical therapy for basal cell carcinoma. A double-blind, randomized, placebo-controlled, parallel group, multicenter study.|year=2008|journal=Int J Dermatol|pmid=18173610|volume=47|issue=1|pages=78–82|url=http://www3.interscience.wiley.com/cgi-bin/fulltext/119389345/PDFSTART|doi=10.1111/j.1365-4632.2007.03363.x}}{{dead link|date=February 2019|bot=medic}}{{cbignore|bot=medic}}
6. ^Solbec Pharmaceuticals. Retrieved on 15 October 2008. {{webarchive |url=https://web.archive.org/web/20080624043122/http://www.solbec.com.au/investorasx.asp?CATEGORY=3 |date=June 24, 2008 }}
7. ^{{cite web|last=Amalfi |first=Carmelo |title=The little mouse who wouldn't say die |publisher=Cosmos Magazine |date=2006-07-06 |url=http://www.cosmosmagazine.com/node/471 |accessdate=2008-10-15 |deadurl=yes |archiveurl=https://web.archive.org/web/20080828212545/http://www.cosmosmagazine.com/node/471 |archivedate=2008-08-28 |df= }}
8. ^{{cite journal |vauthors=Millward M, Powell A, Tyson S, Daly P, Ferguson R, Carter S |title=Phase I trial of coramsine SBP002 in patients with advanced solid tumors. Abstract of presentation at 2005 ASCO Annual Meeting. |url=http://meeting.jco.org/cgi/content/abstract/23/16_suppl/3105 |accessdate=2008-10-15 |journal=J. Clin. Oncol. |year=2005 |volume=23 |issue=16_suppl |pages=3105 |archive-url=https://web.archive.org/web/20081202115110/http://meeting.jco.org/cgi/content/abstract/23/16_suppl/3105 |archive-date=2008-12-02 |dead-url=yes |df= }}
9. ^{{cite journal|journal=Chem Pharm Bull|year=2006|volume=54|issue=2|pages=230–3|title=Steroidal glycosides from the underground parts of Solanum sodomaeum.|vauthors=Ono M, Nishimura K, Suzuki K, Fukushima T, Igoshi K, Yoshimitsu H, Ikeda T, Nohara T|pmid=16462070|doi=10.1248/cpb.54.230}}
10. ^{{cite journal|vauthors=Lee KR, Kozukue N, Han JS, Park JH, Chang EY, Baek EJ, Chang JS, Friedman M|journal=Journal of Agricultural and Food Chemistry|year=2004|volume=52|issue=10|pages=2832–9|title=Glycoalkaloids and metabolites inhibit the growth of human colon (HT29) and liver (HepG2) cancer cells|pmid=15137822|doi=10.1021/jf030526d}}
11. ^{{cite web | url = http://www.fda.gov/orphan/designat/list.xls | title = Developing Products for Rare Diseases & Conditions | publisher = U.S. Food and Drug Administration | accessdate = 15 October 2008}}
12. ^{{cite web|title=coramsinetechnologylicence2104|09.pdf|url=http://www.freedomeye.com.au/index.php?option=com_phocadownload&view=category&id=1:updates&Itemid=74}} {{dead link|date=July 2012}}
13. ^{{cite journal |vauthors=van der Most RG, Himbeck R, Aarons S, Carter SJ, Larma I, Robinson C, Currie A, Lake RA |title=Antitumor efficacy of the novel chemotherapeutic agent coramsine is potentiated by cotreatment with CpG-containing oligodeoxynucleotides|journal=J Immunother. |volume=29 |issue=2 |pages=134–42 |year=2006 |pmid= 16531814 |doi=10.1097/01.cji.0000187958.38179.a9}}
14. ^{{Cite patent | invent1 = Lipscombe, Richard J | invent2 = Carthr, Stephen J |invent3 = Ruane, Michael| date = 2008-03-23 | title = Rhamnose binding protein | country = US | number = 7348152}}
15. ^{{cite web|url=http://solbec.com.au/general.asp?PAGE_ID=41 |title=Coramsine - Other Applications |accessdate=2008-10-31 |deadurl=yes |archiveurl=https://web.archive.org/web/20080719154119/http://www.solbec.com.au/general.asp?PAGE_ID=41 |archivedate=July 19, 2008 }}