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| {{Drugbox | | __NOTOC__ |
| | IUPAC_name = Isopropyl (2''S'')-2-<nowiki>[[[</nowiki>(2''R'',3''R'',4''R'',5''R'')-5-(2,4-dioxopyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydrofuran-2-yl]methoxy-phenoxy-phosphoryl]amino]propanoate
| | {{Sofosbuvir}} |
| | image = PSI-7977.svg
| | {{CMG}} |
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| | imagename = <!-- else may use drug_name -->
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| <!-- Clinical data --> | | ==Overview== |
| | tradename = Sovaldi, Virunon | | '''Simeprevir''' (formerly '''TMC435'''; trade name '''Olysio''') is a drug for the treatment and cure of [[hepatitis C]].<ref>[http://www.nature.com/news/united-states-to-approve-potent-oral-drugs-for-hepatitis-c-1.14059 News: United States to approve potent oral drugs for hepatitis C,] Sara Reardon, Nature, 30 October 2013</ref> It was [[drug development|developed]] by '''Sofosbuvir''' (brand names '''Sovaldi''' and '''Virunon''') is a drug used for [[hepatitis C]] virus (HCV) infection, with a high cure rate.<ref>[http://www.nature.com/news/united-states-to-approve-potent-oral-drugs-for-hepatitis-c-1.14059 News: United States to approve potent oral drugs for hepatitis C,] Sara Reardon, Nature, 30 October 2013</ref><ref name="pmid20845908">{{cite journal | author = Sofia MJ, Bao D, Chang W, Du J, Nagarathnam D, Rachakonda S, Reddy PG, Ross BS, Wang P, Zhang HR, Bansal S, Espiritu C, Keilman M, Lam AM, Steuer HM, Niu C, Otto MJ, Furman PA | title = Discovery of a β-d-2'-deoxy-2'-α-fluoro-2'-β-C-methyluridine nucleotide prodrug (PSI-7977) for the treatment of hepatitis C virus | journal = J. Med. Chem. |volume = 53 | issue = 19 | pages = 7202–18 | year = 2010 | month = October | pmid = 20845908 | doi = 10.1021/jm100863x }}</ref> It inhibits the [[RNA polymerase]] that the hepatitis C virus uses to replicate its RNA. It was discovered at [[Pharmasset]] and [[drug development|developed]] by [[Gilead Sciences]].<ref>{{cite web | url = http://www.gilead.com/pipeline | title = PSI-7977 | publisher = Gilead Sciences}}</ref> |
| | Drugs.com =
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| | MedlinePlus =
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| | licence_EU = <!-- EMA requires brand name -->
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| | licence_US = Sofosbuvir
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| | DailyMedID = <!-- preference to licence_US -->
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| | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
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| | pregnancy_US = B
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| | pregnancy_category= | |
| | legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
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| | legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
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| | legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM -->
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| | legal_US = Rx-only | |
| | legal_status = | |
| | dependency_liability = | |
| | routes_of_administration = | |
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| <!-- Pharmacokinetic data -->
| | Sofosbuvir is the first all-oral, [[Interferon]]-free regimen approved for treating chronic Hepatitis C.<ref name="medscape">{{cite web | url =http://www.medscape.com/viewarticle/817371 | title = FDA Approves 'Game Changer' Hepatitis C Drug Sofosbuvir| author = Tucker M | date = December 6, 2013| publisher = Medscape}}</ref> |
| | bioavailability = | |
| | protein_bound = | |
| | metabolism = | |
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| | excretion = | |
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| <!-- Identifiers --> | | In 2013, the [[FDA]] approved sofosbuvir in combination with [[ribavirin]] (RBV) for oral dual therapy of HCV genotypes 2 and 3, and for triple therapy with injected pegylated interferon (pegIFN) and RBV for treatment-naive patients with HCV genotypes 1 and 4.<ref name="medscape"/> Sofosbuvir treatment regimens last 12 weeks for genotypes 1, 2 and 4, compared to 24 weeks for treatment of genotype 3.<ref>{{cite web | url =http://www.gilead.com/news/press-releases/2013/12/us-food-and-drug-administration-approves-gileads-sovaldi-sofosbuvir-for-the-treatment-of-chronic-hepatitis-c | title = U.S. Food and Drug Administration Approves Gilead’s Sovaldi™ (Sofosbuvir) for the Treatment of Chronic Hepatitis C - See more at:http://www.gilead.com/news/press-releases/2013/12/us-food-and-drug-administration-approves-gileads-sovaldi-sofosbuvir-for-the-treatment-of-chronic-hepatitis-c#sthash.T9uTbSWK.dpuf | date = December 6, 2013| publisher = Gilead}}</ref> Sofosbuvir will cost $84,000 for 12 weeks of treatment and $168,000 for the 24 weeks, which some patient advocates have criticized as unaffordable. |
| | CAS_number = 1190307-88-0 | |
| | CASNo_Ref = {{cascite|correct|}} | |
| | CAS_supplemental =
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| | ATCvet =
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| | ATC_prefix = J05
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| | ATC_suffix = AB
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| | ATC_supplemental =
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| | PubChem =
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| | IUPHAR_ligand =
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| | DrugBank =
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| | ChemSpiderID = 26286922
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| | UNII_Ref = {{fdacite|correct|FDA}}
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| | UNII = WJ6CA3ZU8B
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| | KEGG =
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| | synonyms = PSI-7977; GS-7977
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| <!-- Chemical data -->
| | Interferon-free therapy for treatment of Hepatitis C eliminates the substantial side-effects associated with use of Interferon. Up to half of Hepatitis C patients cannot tolerate the use of Interferon.<ref name="news medical">{{cite web | url = http://www.news-medical.net/news/20130425/Sofosbuvir-is-safer-than-interferon-for-hepatitis-C-patients-say-scientists.aspx | title = Sofosbuvir is safer than interferon for hepatitis C patients, say scientists |date = April 25, 2013| publisher = News Medical}}</ref> |
| | chemical_formula =
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| | C=22 | H=29 | F=1 | N=3 | O=9 | P=1
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| | molecular_weight =
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| | smiles = C[C@@H](C(=O)OC(C)C)N[P@](=O)(OC[C@@H]1[C@H]([C@@]([C@@H](O1)n2ccc(=O)[nH]c2=O)(C)F)O)Oc3ccccc3
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| | InChI = 1/C22H29FN3O9P/c1-13(2)33-19(29)14(3)25-36(31,35-15-8-6-5-7-9-15)32-12-16-18(28)22(4,23)20(34-16)26-11-10-17(27)24-21(26)30/h5-11,13-14,16,18,20,28H,12H2,1-4H3,(H,25,31)(H,24,27,30)/t14-,16+,18+,20+,22+,36-/m0/s1
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| | InChIKey = TTZHDVOVKQGIBA-IQWMDFIBBF | |
| | StdInChI = 1S/C22H29FN3O9P/c1-13(2)33-19(29)14(3)25-36(31,35-15-8-6-5-7-9-15)32-12-16-18(28)22(4,23)20(34-16)26-11-10-17(27)24-21(26)30/h5-11,13-14,16,18,20,28H,12H2,1-4H3,(H,25,31)(H,24,27,30)/t14-,16+,18+,20+,22+,36-/m0/s1 | |
| | StdInChIKey = TTZHDVOVKQGIBA-IQWMDFIBSA-N | |
| }} | |
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| '''Sofosbuvir''' (brand names '''Sovaldi''' and '''Virunon''') is a drug used for [[hepatitis C]] virus (HCV) infection, with a high cure rate.<ref>[http://www.nature.com/news/united-states-to-approve-potent-oral-drugs-for-hepatitis-c-1.14059 News: United States to approve potent oral drugs for hepatitis C,] Sara Reardon, Nature, 30 October 2013</ref><ref name="pmid20845908">{{cite journal | author = Sofia MJ, Bao D, Chang W, Du J, Nagarathnam D, Rachakonda S, Reddy PG, Ross BS, Wang P, Zhang HR, Bansal S, Espiritu C, Keilman M, Lam AM, Steuer HM, Niu C, Otto MJ, Furman PA | title = Discovery of a β-d-2'-deoxy-2'-α-fluoro-2'-β-C-methyluridine nucleotide prodrug (PSI-7977) for the treatment of hepatitis C virus | journal = J. Med. Chem. | volume = 53 | issue = 19 | pages = 7202–18 | year = 2010 | month = October | pmid = 20845908 | doi = 10.1021/jm100863x }}</ref> It inhibits the [[RNA polymerase]] that the hepatitis C virus uses to replicate its RNA. It was discovered at [[Pharmasset]] and [[drug development|developed]] by [[Gilead Sciences]].<ref>{{cite web | url = http://www.gilead.com/pipeline | title = PSI-7977 | publisher = Gilead Sciences}}</ref>
| | ==Category== |
| | Antiviral |
| | ==US Brand Names== |
| | SOVALDI<sup>®</sup> |
| | ==FDA Package Insert== |
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| Sofosbuvir is the first all-oral, [[Interferon]]-free regimen approved for treating chronic Hepatitis C.<ref name="medscape">{{cite web | url = http://www.medscape.com/viewarticle/817371 | title = FDA Approves 'Game Changer' Hepatitis C Drug Sofosbuvir| author = Tucker M | date = December 6, 2013| publisher = Medscape}}</ref> | | ''' [[Sofosbuvir description|Description]]''' |
| | '''| [[Sofosbuvir clinical pharmacology|Clinical Pharmacology]]''' |
| | '''| [[Sofosbuvir microbiology|Microbiology]]''' |
| | '''| [[Sofosbuvir indications and usage|Indications and Usage]]''' |
| | '''| [[Sofosbuvir contraindications|Contraindications]]''' |
| | '''| [[Sofosbuvir warnings and precautions|Warnings and Precautions]]''' |
| | '''| [[Sofosbuvir adverse reactions|Adverse Reactions]]''' |
| | '''| [[Sofosbuvir drug interactions|Drug Interactions]]''' |
| | '''| [[Sofosbuvir overdosage|Overdosage]]''' |
| | '''| [[Sofosbuvir clinical studies|Clinical Studies]]''' |
| | '''| [[Sofosbuvir dosage and administration|Dosage and Administration]]''' |
| | '''| [[Sofosbuvir how supplied|How Supplied]]''' |
| | '''| [[Sofosbuvir labels and packages|Labels and Packages]]''' |
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| In 2013, the [[FDA]] approved sofosbuvir in combination with [[ribavirin]] (RBV) for oral dual therapy of HCV genotypes 2 and 3, and for triple therapy with injected pegylated interferon (pegIFN) and RBV for treatment-naive patients with HCV genotypes 1 and 4.<ref name="medscape"/> Sofosbuvir treatment regimens last 12 weeks for genotypes 1, 2 and 4, compared to 24 weeks for treatment of genotype 3.<ref>{{cite web | url = http://www.gilead.com/news/press-releases/2013/12/us-food-and-drug-administration-approves-gileads-sovaldi-sofosbuvir-for-the-treatment-of-chronic-hepatitis-c | title = U.S. Food and Drug Administration Approves Gilead’s Sovaldi™ (Sofosbuvir) for the Treatment of Chronic Hepatitis C - See more at: http://www.gilead.com/news/press-releases/2013/12/us-food-and-drug-administration-approves-gileads-sovaldi-sofosbuvir-for-the-treatment-of-chronic-hepatitis-c#sthash.T9uTbSWK.dpuf | date = December 6, 2013| publisher = Gilead}}</ref> Sofosbuvir will cost $84,000 for 12 weeks of treatment and $168,000 for the 24 weeks, which some patient advocates have criticized as unaffordable.
| | ==Mechanism of Action== |
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| Interferon-free therapy for treatment of Hepatitis C eliminates the substantial side-effects associated with use of Interferon. Up to half of Hepatitis C patients cannot tolerate the use of Interferon.<ref name="news medical">{{cite web | url = http://www.news-medical.net/news/20130425/Sofosbuvir-is-safer-than-interferon-for-hepatitis-C-patients-say-scientists.aspx | title = Sofosbuvir is safer than interferon for hepatitis C patients, say scientists | date = April 25, 2013| publisher = News Medical}}</ref>
| | ==References== |
| | {{Reflist|2}} |
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| == Mechanism of Action ==
| | [[Category:Antibiotics]] |
| | | [[Category:Wikinfect]] |
| Sofosbuvir is a [[prodrug]] that is metabolized to the active antiviral agent 2'-deoxy-2'-α-fluoro-β-''C''-methyluridine-5'-monophosphate.<ref name="pmid20801890">{{cite journal | author = Murakami E, Tolstykh T, Bao H, Niu C, Steuer HM, Bao D, Chang W, Espiritu C, Bansal S, Lam AM, Otto MJ, Sofia MJ, Furman PA | title = Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977 | journal = J. Biol. Chem. | volume = 285 | issue = 45 | pages = 34337–47 | year = 2010 | month = November | pmid = 20801890 | pmc = 2966047 | doi = 10.1074/jbc.M110.161802 }}</ref> Sofosbuvir is a nucleotide analogue inhibitor of the hepatitis C virus (HCV) polymerase.<ref>{{cite web | url = http://hepaton.com/272/sofosbuvir | title = Sofosbuvir | author = Alejandro Soza | date = November 11, 2012 | publisher = Hepaton}}</ref> The HCV polymerase or NS5B protein is a RNA-dependent RNA polymerase critical for the viral cycle.
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| == FDA Approval ==
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| The [[New Drug Application]] for Sofosbuvir was submitted on April 8, 2013 and received the FDA's Breakthrough Therapy Designation, which grants priority review status to drug candidates that may offer major treatment advantages over existing options.<ref>{{cite web | url = http://www.drugs.com/nda/sofosbuvir_131025.html | title = FDA Advisory Committee Supports Approval of Gilead’s Sofosbuvir for Chronic Hepatitis C Infection | date = October 25, 2013 | publisher = ''Drugs.com''}}</ref>
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| On 6<sup>th</sup> December 2013, the U.S. [[Food and Drug Administration]] approved Sovaldi for the treatment of chronic hepatitis C.<ref name="urlFDA approves Sovaldi for chronic hepatitis C">{{cite web | url = http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm377888.htm | title = FDA approves Sovaldi for chronic hepatitis C | date = 2013-12-06| work = FDA New Release | publisher = U.S. Food and Drug Administration }}</ref>
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| == Medical uses ==
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| Sofosbuvir is being studied in combination with [[pegylated interferon]] and [[ribavirin]], with ribavirin alone, and with other direct-acting antiviral agents.<ref>{{cite web | url = http://www.businessweek.com/ap/financialnews/D9R58SUO2.htm | title = Gilead Sciences to buy Pharmasset for $11 billion | author = Murphy T | date = November 21, 2011 | publisher = ''[[Bloomberg Businessweek]]''}}</ref><ref name="pmid24289735">{{cite journal | author = Asselah T | title = Sofosbuvir for the treatment of hepatitis C virus | journal = Expert Opin Pharmacother | volume = 15 | issue = 1 | pages = 121–30 | year = 2014 | month = January | pmid = 24289735 | doi = 10.1517/14656566.2014.857656 }}</ref> It has shown clinical efficacy when used either with pegylated interferon/ribavirin or in interferon-free combinations. In particular, combinations of sofosbuvir with NS5A inhibitors, such as [[daclatasvir]] or [[GS-5885]], have shown sustained virological response rates of up to 100% in people infected with HCV.<ref name="urlAASLD 2012: Sofosbuvir and daclatasvir dual regimen cures most people with HCV genotypes 1, 2, or 3 - ELPA - European Liver Patients Association">{{cite web | url = http://www.elpa-info.org/elpa-news---reader/items/aasld-2012-sofosbuvir-and-daclatasvir-dual-regimen-cures-most-people-with-hcv-genotypes-1-2-or-3.htm | title = AASLD 2012: Sofosbuvir and daclatasvir dual regimen cures most people with HCV genotypes 1, 2, or 3 | author = | date = 2012-11-21 | work = News | publisher = European Liver Patients Association }}</ref>
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| Data from the ELECTRON trial showed that a dual interferon-free regimen of sofosbuvir plus ribavirin produced a 24-week post-treatment sustained virological response (SVR24) rate of 100% for previously untreated patients with HCV genotypes 2 or 3.<ref>[http://hivandhepatitis.com/hepatitis-c/hepatitis-c-topics/hcv-treatment/3336-aasld-psi-7977-plus-ribavirin-can-cure-hepatitis-c-in-12-weeks-without-interferon AASLD: PSI-7977 plus Ribavirin Can Cure Hepatitis C in 12 Weeks without Interferon]. Highleyman, L. HIVandHepatitis.com. 8 November 2011.</ref><ref name="pmid23281974">{{cite journal | author = Gane EJ, Stedman CA, Hyland RH, Ding X, Svarovskaia E, Symonds WT, Hindes RG, Berrey MM | title = Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C | journal = N. Engl. J. Med. | volume = 368 | issue = 1 | pages = 34–44 | year = 2013 | month = January | pmid = 23281974 | doi = 10.1056/NEJMoa1208953 }}</ref>
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| Data presented at the 20th Conference on Retroviruses and Opportunistic Infections in March 2013 showed that a triple regimen of sofosbuvir, [[ledipasvir]], and ribavirin produced a 12-week post-treatment sustained virological response (SVR12) rate of 100% for both treatment-naive patients and prior non-responders with HCV genotype 1.<ref>[http://www.hivandhepatitis.com/hcv-treatment/experimental-hcv-drugs/4005-croi-2013-sofosbuvirledipasvirribavirin-combo-for-hcv-produces-100-sustained-response CROI 2013: Sofosbuvir + Ledipasvir + Ribavirin Combo for HCV Produces 100% Sustained Response]. Highleyman, L. HIVandHepatitis.com. 4 March 2013.</ref> Gilead has developed a sofosbuvir + ledipasvir coformulation that is being tested with and without ribavirin.
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| == Cost ==
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| Sofosbuvir will cost $84,000 for 12 weeks of treatment used for genotype 1 and 2, and $168,000 for the 24 weeks used for genotype 3.<ref name="urlF.D.A. Approves Pill to Treat Hepatitis C - NYTimes.com">{{cite web | url = http://www.nytimes.com/2013/12/07/business/fda-approves-pill-to-treat-hepatitis-c.html+ | title = F.D.A. Approves Pill to Treat Hepatitis C | author = Pollack A | date = December 6, 2013 | work = | publisher = NYTimes.com }}</ref> This represents a substantial pricing increase from previous treatments consisting of Interferon and Ribavirin, which were valued between 15,000-20,000 dollars.<ref name="motley fool">{{cite web | url = http://www.fool.com/investing/general/2013/12/11/gileads-sofosbuvir-gets-new-name-price-headaches.aspx | title = Gilead's Sofosbuvir Gets New Name, Price, Headaches | author = Campbell T | date = December 11, 2013 | publisher = The Motley Fool }}</ref> The price is also significantly higher than that of [[Johnson & Johnson]]'s recently approved drug [[Olysio]], which is valued at $50,000 and also treats chronic Hepatitis C.<ref name="motley fool"/> The high cost of the drug has resulted in a push back from insurance companies and the like, including [[Express Scripts]], which has threatened to substitute lower priced competitors, even if those therapies come with a more unfriendly dosing schedule.<ref name="motley fool"/> Other treatments that have recently entered the market have not matched the efficacy of Sofosbuvir, however, allowing Gilead to name its price until additional competition enters the market.<ref name="motley fool"/> Patient advocates such as Doctors Without Borders have complained about the price, which is particularly difficult for underdeveloped countries to afford.<ref>[http://www.sciencemag.org/content/342/6164/1302.full Advocates Protest the Cost of a Hepatitis C Cure,] Jon Cohen, Science, 13 December 2013:Vol. 342 no. 6164 pp. 1302-1303 DOI: 10.1126/science.342.6164.1302</ref>
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| = Information about related patents =
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| Patents: US patent number 7964580, US patent number 8415322, US patent number 8334270,US patent number 7429572
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| Patent Expiration Date: March 26, 2029 for US patent number 7964580 and 8334270 (2028 in EU)； April 3, 2025 for US patent number 7429572 and 8415322
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| = References =
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| {{reflist}}
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| [[Category:Prodrugs]]
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| [[Category:Anti-RNA virus drugs]]
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| [[Category:Hepatitis C]]
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| [[Category:Pyrimidinediones]]
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| [[Category:Organofluorides]] | |
| [[Category:Propionates]] | |