elbasvir

{{short description|Chemical compound}}

{{Drugbox

| IUPAC_name = Dimethyl N,N’-([(6S)-6H-indolo[1,2-c] [1,3]benzoxazine-3,10-diyl]bis{1H-imidazole-5,2-diyl-(2S)-pyrrolidine-2,1-diyl[(2S)-1-oxo-3-methylbutane-1,2-diyl]})biscarbamate

| image = File:Elbasvir.svg

| width = 350

| tradename = Zepatier (combination with grazoprevir)

| Drugs.com =

| MedlinePlus =

| pregnancy_AU =

| pregnancy_US =

| pregnancy_category =

| licence_EU = yes

| legal_AU =

| legal_CA =

| legal_UK =

| legal_US =

| legal_status = Rx-only

| routes_of_administration = Oral

| bioavailability =

| protein_bound = >99.9%

| metabolism = CYP3A4

| elimination_half-life = 24 hours

| excretion = >90% via faeces, <1% via urine

| CAS_number = 1370468-36-2

| ATCvet =

| ATC_prefix = J05

| ATC_suffix = AP10

| ATC_supplemental =
{{ATC|J05|AP54}} (combination with grazoprevir)

| PubChem = 71661251

| DrugBank = DB11574

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 632L571YDK

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 132967

| ChemSpiderID = 30843797

| KEGG = D10625

| synonyms = MK-8742

| C=49 | H=55 | N=9 | O=7

| smiles = CC(C)[C@@H](C(=O)N1CCC[C@H]1c2[nH]cc(n2)c3ccc4c(c3)cc-5n4[C@@H](Oc6c5ccc(c6)c7c[nH]c(n7)[C@@H]8CCCN8C(=O)[C@H](C(C)C)NC(=O)OC)c9ccccc9)NC(=O)OC

| StdInChI = 1S/C49H55N9O7/c1-27(2)41(54-48(61)63-5)45(59)56-20-10-14-37(56)43-50-25-34(52-43)30-17-19-36-32(22-30)23-39-33-18-16-31(24-40(33)65-47(58(36)39)29-12-8-7-9-13-29)35-26-51-44(53-35)38-15-11-21-57(38)46(60)42(28(3)4)55-49(62)64-6/h7-9,12-13,16-19,22-28,37-38,41-42,47H,10-11,14-15,20-21H2,1-6H3,(H,50,52)(H,51,53)(H,54,61)(H,55,62)/t37-,38-,41-,42-,47-/m0/s1

| StdInChIKey = BVAZQCUMNICBAQ-PZHYSIFUSA-N

}}

Elbasvir is a drug approved by the FDA in January 2016[https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm483828.htm FDA approves Zepatier for treatment of chronic hepatitis C genotypes 1 and 4. January 28, 2016] for the treatment of hepatitis C. It was developed by Merck and completed Phase III trials, used in combination with the NS3/4A protease inhibitor grazoprevir under the trade name Zepatier, either with or without ribavirin.{{cite journal | vauthors = Lawitz E, Gane E, Pearlman B, Tam E, Ghesquiere W, Guyader D, Alric L, Bronowicki JP, Lester L, Sievert W, Ghalib R, Balart L, Sund F, Lagging M, Dutko F, Shaughnessy M, Hwang P, Howe AY, Wahl J, Robertson M, Barr E, Haber B | display-authors = 6 | title = Efficacy and safety of 12 weeks versus 18 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin for hepatitis C virus genotype 1 infection in previously untreated patients with cirrhosis and patients with previous null response with or without cirrhosis (C-WORTHY): a randomised, open-label phase 2 trial | journal = Lancet | volume = 385 | issue = 9973 | pages = 1075–86 | date = March 2015 | pmid = 25467591 | doi = 10.1016/S0140-6736(14)61795-5 }}

Elbasvir is a highly potent and selective NS5A inhibitor of the hepatitis C virus NS5A replication complex.{{cite journal | vauthors = Coburn CA, Meinke PT, Chang W, Fandozzi CM, Graham DJ, Hu B, Huang Q, Kargman S, Kozlowski J, Liu R, McCauley JA, Nomeir AA, Soll RM, Vacca JP, Wang D, Wu H, Zhong B, Olsen DB, Ludmerer SW | display-authors = 6 | title = Discovery of MK-8742: an HCV NS5A inhibitor with broad genotype activity | journal = ChemMedChem | volume = 8 | issue = 12 | pages = 1930–40 | date = December 2013 | pmid = 24127258 | doi = 10.1002/cmdc.201300343 | s2cid = 10543092 | doi-access = free }} It has only been investigated as a combination product with other complementary hepatitis C antiviral drugs such as grazoprevir and MK-3682, and it is unclear whether elbasvir would show robust antiviral activity if it was administered by itself. Nevertheless, combination products of this type represent the most successful approach yet developed for actually curing hepatitis C, rather than merely slowing the progression of the disease.{{cite journal | vauthors = Gentile I, Buonomo AR, Zappulo E, Borgia G | title = Interferon-free therapies for chronic hepatitis C: toward a hepatitis C virus-free world? | journal = Expert Review of Anti-Infective Therapy | volume = 12 | issue = 7 | pages = 763–73 | date = July 2014 | pmid = 24918116 | doi = 10.1586/14787210.2014.929497 | s2cid = 207199323 }}