WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 202540
Description: Rubitecan is a semisynthetic agent related to camptothecin with potent antitumor and antiviral properties. Rubitecan binds to and inhibits the enzyme topoisomerase I and induces protein-linked DNA single-strand breaks, thereby blocking DNA and RNA synthesis in dividing cells; this agent also prevents repair of reversible single-strand DNA breaks.
MedKoo Cat#: 202540
Chemical Formula: C20H15N3O6
Exact Mass: 393.09609
Molecular Weight: 393.35
Elemental Analysis: C, 61.07; H, 3.84; N, 10.68; O, 24.40
Synonym: RFS 2000; RFS-2000; RFS2000; Abbreviation: 9NC. 9-nitro-camptothecin; 9-nitro-CPT; nitrocamptothecin. US brand names: Camptogen; Orathecin.
IUPAC/Chemical Name: (S)-4-ethyl-4-hydroxy-10-nitro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione
InChi Key: VHXNKPBCCMUMSW-FQEVSTJZSA-N
InChi Code: InChI=1S/C20H15N3O6/c1-2-20(26)13-7-16-17-10(8-22(16)18(24)12(13)9-29-19(20)25)6-11-14(21-17)4-3-5-15(11)23(27)28/h3-7,26H,2,8-9H2,1H3/t20-/m0/s1
SMILES Code: O=C1[C@](O)(CC)C2=C(CO1)C(N3CC4=CC5=C([N+]([O-])=O)C=CC=C5N=C4C3=C2)=O
According to BioSpace, EuroGen Pharmaceuticals Ltd. has withdrawn its Marketing Authorisation Application for OrathecinÂ™ (rubitecan), following discussions with the EMEA. Orathecin is a topoisomerase I inhibitor under development for the treatment of pancreatic cancer in patients who have failed at least one prior chemotherapy regimen. According to a press release from the EMEA, the Committee for Medicinal Products for Human Use (CHMP) reviewed Phase III data submitted as part of the application and did not consider it to be sufficient to demonstrate a clinical benefit for patients receiving Orathecin. The Company could not address the issues raised at this stage and therefore withdrew the application. Orathecin has orphan drug status in both the US and the EU. An ongoing US Phase II trial is looking at a combination of Orathecin and gemcitabine as a first-line combination therapy for advanced pancreatic cancer patients who are chemotherapy naive. See: http://www.nelm.nhs.uk/en/NeLM-Area/News/486153/486361/486372/ .
1: Caponigro F, Cartenì G, Droz JP, Milano A, Davis WB, Pollard P. Phase II study of rubitecan in recurrent or metastatic head and neck cancer. Cancer Chemother Pharmacol. 2008 Jul;62(2):209-14. Epub 2007 Sep 19. PubMed PMID: 17882418.
2: Patel H, Stoller R, Auber M, Potter D, Cai C, Zamboni W, Kiefer G, Matin K, Schmotzer A, Ramanathan RK. Phase II study of rubitecan, an oral camptothecin in patients with advanced colorectal cancer who have failed previous 5-fluorouracil based chemotherapy. Invest New Drugs. 2006 Jul;24(4):359-63. PubMed PMID: 16525767.
3: Clark JW. Rubitecan. Expert Opin Investig Drugs. 2006 Jan;15(1):71-9. Review. PubMed PMID: 16370935.
4: Chedid S, Rivera E, Frye DK, Ibrahim N, Esteva F, Valero V, Hortobagyi G, Mettinger KL, Cristofanilli M. Minimal clinical benefit of single agent Orathecin (Rubitecan) in heavily pretreated metastatic breast cancer. Cancer Chemother Pharmacol. 2006 Apr;57(4):540-4. Epub 2005 Sep 29. PubMed PMID: 16193332.
5: Baka S, Ranson M, Lorigan P, Danson S, Linton K, Hoogendam I, Mettinger K, Thatcher N. A phase II trial with RFS2000 (rubitecan) in patients with advanced non-small cell lung cancer. Eur J Cancer. 2005 Jul;41(11):1547-50. PubMed PMID: 16026691.
6: Burris HA 3rd, Rivkin S, Reynolds R, Harris J, Wax A, Gerstein H, Mettinger KL, Staddon A. Phase II trial of oral rubitecan in previously treated pancreatic cancer patients. Oncologist. 2005 Mar;10(3):183-90. PubMed PMID: 15793221.
7: Rubitecan: 9-NC, 9-Nitro-20(S)-camptothecin, 9-nitro-camptothecin, 9-nitrocamptothecin, RFS 2000, RFS2000. Drugs R D. 2004;5(5):305-11. PubMed PMID: 15357630.
8: Schoemaker NE, Mathôt RA, Schöffski P, Rosing H, Schellens JH, Beijnen JH. Development of an optimal pharmacokinetic sampling schedule for rubitecan administered orally in a daily times five schedule. Cancer Chemother Pharmacol. 2002 Dec;50(6):514-7. Epub 2002 Nov 5. PubMed PMID: 12451480.
9: Fracasso PM, Rader JS, Govindan R, Herzog TJ, Arquette MA, Denes A, Mutch DG, Picus J, Tan BR, Fears CL, Goodner SA, Sun SL. Phase I study of rubitecan and gemcitabine in patients with advanced malignancies. Ann Oncol. 2002 Nov;13(11):1819-25. PubMed PMID: 12419757.
10: Sands H, Mishra A, Stoeckler JD, Hollister B, Chen SF. Preclinical activity of an i.v. formulation of rubitecan in IDD-P against human solid tumor xenografts. Anticancer Drugs. 2002 Oct;13(9):965-75. PubMed PMID: 12394260.
11: Schöffski P, Herr A, Vermorken JB, Van den Brande J, Beijnen JH, Rosing H, Volk J, Ganser A, Adank S, Botma HJ, Wanders J. Clinical phase II study and pharmacological evaluation of rubitecan in non-pretreated patients with metastatic colorectal cancer-significant effect of food intake on the bioavailability of the oral camptothecin analogue. Eur J Cancer. 2002 Apr;38(6):807-13. PubMed PMID: 11937315.
12: Giovanella BC, Stehlin JS, Hinz HR, Kozielski AJ, Harris NJ, Vardeman DM. Preclinical evaluation of the anticancer activity and toxicity of 9-nitro-20(S)-camptothecin (Rubitecan). Int J Oncol. 2002 Jan;20(1):81-8. PubMed PMID: 11743646.
13: Kemp KR, Liehr JG, Giovanella B. Combined radiation and 9-nitrocamptothecin (rubitecan) in the treatment of locally advanced pancreatic cancer. Ann N Y Acad Sci. 2000;922:320-3. PubMed PMID: 11193912.