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{{Short description|Chemical compound}} |
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{{Drugbox |
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{{Drugbox |
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| IUPAC_name = (4''S'')-4-ethyl-4-hydroxy-11-nitro-1''H''-pyranoindolizinoquinoline-3,14(4''H'',12''H'')-dione |
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|synonyms = <small>(19''S'')-19-ethyl-19-hydroxy-10-nitro-17-oxa-3,13-diazapentacyclohenicosa-1(21),2,4,6,8,10,15(20)-heptaene-14,18-dione</small> |
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| verifiedrevid = 376278337 |
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| image = Rubitecan.png |
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| IUPAC_name = (4''S'')-4-Ethyl-4-hydroxy-11-nitro-1''H''-pyranoindolizinoquinoline-3,14(4''H'',12''H'')-dione |
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| CAS_number = 91421-42-0 |
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| image = Rubitecan.svg |
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| ATC_prefix = none |
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| ATC_suffix = |
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<!--Clinical data--> |
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| PubChem = 11954380 |
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| tradename = Orathecin |
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| DrugBank = |
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| C = 20 |H = 15 |N = 3 |O = 6 |
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| molecular_weight = 393.349 ]/] |
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| bioavailability = |
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| protein_bound = |
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| metabolism = |
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| elimination_half-life = |
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| excretion = |
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| pregnancy_category = |
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| pregnancy_category = |
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| legal_status = |
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| legal_status = Application withdrawn |
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| routes_of_administration = Oral |
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| routes_of_administration = Oral (]) |
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<!--Pharmacokinetic data--> |
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| bioavailability = 25–30% (rubitecan and 9-AC; in dogs) |
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| protein_bound = 97% (rubitecan), 65% (9-AC) |
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| metabolism = Probably ]-dependent |
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| metabolites = 9-Aminocamptothecin (9-AC) |
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| elimination_half-life = 15–18 hours (rubitecan), 18–22 hours (9-AC) |
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| excretion = ] and ] (major proportion), ] (the minor one)<ref>{{cite web|title=Withdrawal Assessment Report for Orathecin (rubitecan). Applicant: EuroGen Pharmaceuticals, Ltd.|url=http://www.ema.europa.eu/docs/en_GB/document_library/Application_withdrawal_assessment_report/2010/01/WC500069806.pdf|publisher=European Medicines Agency|access-date=15 July 2016|pages=4–8|date=30 November 2007}}</ref> |
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<!--Identifiers--> |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 91421-42-0 |
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| ATC_prefix = None |
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| ATC_suffix = |
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| PubChem = 472335 |
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| DrugBank = |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ChemSpiderID = 414807 |
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| UNII_Ref = {{fdacite|changed|FDA}} |
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| UNII = H19C446XXB |
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| ChEBI_Ref = {{ebicite|changed|EBI}} |
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| ChEBI = 90225 |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = 77305 |
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| KEGG_Ref = {{keggcite|changed|kegg}} |
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| KEGG = D04031 |
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<!--Chemical data--> |
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| C=20 | H=15 | N=3 | O=6 |
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| synonyms = 9-Nitrocamptothecin<br>9-NC<br>9-nitro-20(S)-camptothecin<br>Camptogen<br>(19''S'')-19-Ethyl-19-hydroxy-10-nitro-17-oxa-3,13-diazapentacyclohenicosa-1(21),2,4,6,8,10,15(20)-heptaene-14,18-dione |
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| smiles = CC1(C2=C(COC1=O)C(=O)N3CC4=CC5=C(C=CC=C5(=O))N=C4C3=C2)O |
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| StdInChI_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChI = 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 |
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| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChIKey = VHXNKPBCCMUMSW-FQEVSTJZSA-N |
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}} |
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'''Rubitecan''' (], marketing name '''Orathecin''') is an oral ] inhibitor, developed by Supergen. |
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'''Rubitecan''' (], marketing name '''Orathecin''') is an oral ] inhibitor, developed by SuperGen (now ''''.; a member of the ''''). |
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==History== |
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==History== |
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On January 27, 2004, Supergen announced that it has completed the submission of an NDA for rubitecan to the US FDA, <ref>{{cite web |url=http://www.drugs.com/nda/orathecin_040128.html |title=Drugs.com, SuperGen completes submission of New Drug Application (NDA) for Orathecin as an oral treatment for pancreatic cancer |accessdate=2008-03-25 |format= |work= }}</ref> and was accepted for filing on March 2004.<ref>{{cite web |url=http://www.drugs.com/nda/orathecin_040326.html |title=Drugs.com, SuperGen’s New Drug Application for Orathecin (rubitecan) capsules accepted by FDA for filing |accessdate=2008-03-25 |format= |work= }}</ref> |
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On January 27, 2004, SuperGen announced that it has completed the submission of an NDA for rubitecan to the US FDA,<ref>{{cite web |url=https://www.drugs.com/nda/orathecin_040128.html | work = Drugs.com | title = SuperGen completes submission of New Drug Application (NDA) for Orathecin as an oral treatment for pancreatic cancer |access-date=2008-03-25 }}</ref> and was accepted for filing in March 2004.<ref>{{cite web |url=https://www.drugs.com/nda/orathecin_040326.html |work = Drugs.com | title = SuperGen's New Drug Application for Orathecin (rubitecan) capsules accepted by FDA for filing |access-date=2008-03-25 }}</ref> |
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On January 2005, Supergen withdrew the NDA for rubitecan, based on feedback indicating that the current data package would not be sufficient to gain US approval,<ref>{{cite web |url=http://www.drugs.com/nda/orathecin_050103.html |title=Drugs.com, SuperGen Announces Withdrawal of Orathecin NDA |accessdate=2008-03-25 |format= |work= }}</ref> and on January 2006, the Marketing Authorization Application (MAA) filed with the ] (EMA) was also withdrawn.<ref>{{cite web |url=http://www.emea.europa.eu/humandocs/PDFs/EPAR/orathecin/2621906en.pdf |title=Press release from the EMEA website regarding withdrawal of Orathecin MAA |accessdate=2008-03-25 |format=PDF |work= }}</ref> |
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In January 2005, and under the direction of then-CEO James Manuso, SuperGen withdrew the NDA for rubitecan, based on feedback indicating that the current data package would not be sufficient to gain US approval,<ref>{{cite web |url=https://www.drugs.com/nda/orathecin_050103.html |work = Drugs.com | title = SuperGen Announces Withdrawal of Orathecin NDA |access-date=2008-03-25 }}</ref> and in January 2006, the Marketing Authorization Application (MAA) filed with the ] (EMA) was also withdrawn.<ref>{{cite web |url=http://www.emea.europa.eu/humandocs/PDFs/EPAR/orathecin/2621906en.pdf |title=Press release from the EMEA website regarding withdrawal of Orathecin MAA |access-date=2008-03-25 |url-status=dead |archive-url=https://web.archive.org/web/20070611123027/http://www.emea.europa.eu/humandocs/PDFs/EPAR/orathecin/2621906en.pdf |archive-date=2007-06-11 }}</ref> |
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The name Rubitecan is a portmanteau of SuperGen's founder, ], and the chemical name 9-Nitrocamptothecin. |
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==References== |
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{{Reflist}} |
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==Synthesis== |
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{{Chemotherapeutic agents}} |
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Large scale production of Rubitecan has encountered problems. The direct nitration of camptothecin results in regioselectivity problems. One way that has been used to synthesize Rubitecan is to nitrate 10-hydroxycamptothecin then remove the hydroxyl functional group.<ref>{{cite journal |title=A Practical Regiospecific Synthesis of 9-Nitrocamptothecin |journal= Synthesis|year=2006 |doi=10.1055/s-2006-942359 | vauthors = Chen Z, Fu Q |volume=2006 |issue=12 |pages=1940–1942 }}</ref> |
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==Use as Anti-Cancer Drug== |
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Rubitecan is a compound used extensively in cancer research. Rubitecan is an effective drug against pancreatic cancer and other solid tumors. One major problem is the lack of oral bioavailability due to low permeability and poor water solubility. One study shows 9-NC-SD through Soluplus1-based solid dispersion system is a much more effective delivery method than free 9-NC.<ref name="pmid25445521">{{cite journal | vauthors = Lian X, Dong J, Zhang J, Teng Y, Lin Q, Fu Y, Gong T | title = Soluplus(®) based 9-nitrocamptothecin solid dispersion for peroral administration: preparation, characterization, in vitro and in vivo evaluation | journal = International Journal of Pharmaceutics | volume = 477 | issue = 1–2 | pages = 399–407 | date = December 2014 | pmid = 25445521 | doi = 10.1016/j.ijpharm.2014.10.055 }}</ref> |
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== References == |
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{{Reflist}} |
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{{Chemotherapeutic agents}} |
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{{antineoplastic-drug-stub}} |
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{{antineoplastic-drug-stub}} |
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