| 词条 | Rubitecan |
| 释义 |
| Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 376278337 | IUPAC_name = (4S)-4-Ethyl-4-hydroxy-11-nitro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione | image = Rubitecan.svg | tradename = Orathecin | pregnancy_category = | legal_status = Application withdrawn | routes_of_administration = Oral (capsules) | bioavailability = 25–30% (rubitecan and 9-AC; in dogs) | protein_bound = 97% (rubitecan), 65% (9-AC) | metabolism = Probably CYP-dependent | metabolites = 9-Aminocamptothecin (9-AC) | elimination_half-life = 15–18 hours (rubitecan), 18–22 hours (9-AC) | excretion = Bile and feces (major proportion), urine (the minor one)[1] | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 91421-42-0 | ATC_prefix = None | ATC_suffix = | PubChem = 472335 | DrugBank = | ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} | ChemSpiderID = 414807 | UNII_Ref = {{fdacite|changed|FDA}} | UNII = H19C446XXB | ChEBI_Ref = {{ebicite|changed|EBI}} | ChEBI = 90225 | ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL = 77305 | KEGG_Ref = {{keggcite|changed|kegg}} | KEGG = D04031 | C=20 | H=15 | N=3 | O=6 | molecular_weight = 393.349 g/mol | synonyms = 9-Nitrocamptothecin 9-NC 9-nitro-20(S)-camptothecin Camptogen (19S)-19-Ethyl-19-hydroxy-10-nitro-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaene-14,18-dione | smiles = CC[C@@]1(C2=C(COC1=O)C(=O)N3CC4=CC5=C(C=CC=C5[N+](=O)[O-])N=C4C3=C2)O | StdInChI_Ref = {{stdinchicite|changed|chemspider}} | 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 | StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} | StdInChIKey = VHXNKPBCCMUMSW-FQEVSTJZSA-N }} Rubitecan (INN, marketing name Orathecin) is an oral topoisomerase inhibitor, developed by Supergen (now Astex Pharmaceuticals, Inc.; a member of the [https://www.otsuka.com/en/ Otsuka Group]). HistoryOn January 27, 2004, Supergen announced that it has completed the submission of an NDA for rubitecan to the US FDA,[2] and was accepted for filing on March 2004.[3] 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,[4] and on January 2006, the Marketing Authorization Application (MAA) filed with the European Medicines Agency (EMA) was also withdrawn.[5] SynthesisLarge scale production of Rubitecan has encountered problems.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 than remove the hydroxyl functional group.[6] Use as Anti-Cancer DrugRubitecan 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.[7] References1. ^{{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|accessdate=15 July 2016|pages=4–8|date=30 November 2007}} {{Chemotherapeutic agents}}{{antineoplastic-drug-stub}}2. ^{{cite web |url=https://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= }} 3. ^{{cite web |url=https://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= }} 4. ^{{cite web |url=https://www.drugs.com/nda/orathecin_050103.html |title=Drugs.com, SuperGen Announces Withdrawal of Orathecin NDA |accessdate=2008-03-25 |format= |work= }} 5. ^{{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= |deadurl=yes |archiveurl=https://web.archive.org/web/20070611123027/http://www.emea.europa.eu/humandocs/PDFs/EPAR/orathecin/2621906en.pdf |archivedate=2007-06-11 |df= }} 6. ^{{cite web |url=http://www.thieme-connect.de/DOI/DOI?10.1055/s-2006-942359 |title=A Practical Regiospecific Synthesis of 9-Nitrocamptothecin |accessdate=2017-10-10 |format=PDF |work= }} 7. ^{{cite web |url=https://ac-els-cdn-com.proxy.library.nd.edu/S0378517314007789/1-s2.0-S0378517314007789-main.pdf?_tid=f70a55d6-b533-11e7-9608-00000aab0f02&acdnat=1508462225_d0142810ffc673735f27e5abeb892f18|title=Soluplus® based 9-nitrocamptothecin solid dispersion for peroral administration |accessdate=2017-10-10 |format=PDF |work= }} 2 : Abandoned drugs|Topoisomerase inhibitors |
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