View source for Chemistry:Bemnifosbuvir

{{Short description|Chemical compound}}
{{Drugbox
| IUPAC_name = Propan-2-yl (2''S'')-2-<nowiki>[[[</nowiki>(2''R'',3''R'',4''R'',5''R'')-5-[2-amino-6-(methylamino)purin-9-yl]-4-fluoro-3-hydroxy-4-methyloxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate
| image = Bemnifosbuvir.svg
<!--Clinical data-->
| tradename =
| legal_US = Investigational New Drug
| legal_status =

<!--Pharmacokinetic data-->
| bioavailability =
| metabolism =
| elimination_half-life =
| excretion =

<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number =  1998705-64-8
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 7UM3SQL968
| CAS_supplemental = <br>2241337-84-6 (hemisulfate)
| PubChem = 122527455
| KEGG = D12255
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| ChemSpiderID = 112747221
| synonyms = AT-527, AT-511

<!--Chemical data-->
| C=24 | H=33 | F=1 | N=7 | O=7 | P=1
| SMILES = C[C@@H](C(=O)OC(C)C)NP(=O)(OC[C@@H]1[C@H]([C@@]([C@@H](O1)N2C=NC3=C(N=C(N=C32)N)NC)(C)F)O)OC4=CC=CC=C4
|  StdInChI = 1S/C24H33FN7O7P/c1-13(2)37-21(34)14(3)31-40(35,39-15-9-7-6-8-10-15)36-11-16-18(33)24(4,25)22(38-16)32-12-28-17-19(27-5)29-23(26)30-20(17)32/h6-10,12-14,16,18,22,33H,11H2,1-5H3,(H,31,35)(H3,26,27,29,30)/t14-,16+,18+,22+,24+,40?/m0/s1
|  StdInChIKey = OISLSHLAXHALQZ-HEOQURLSSA-N
}}

'''Bemnifosbuvir''' ('''AT-527''', '''RO7496998''') is an [[Biology:Antiviral drug|antiviral drug]] invented by Atea Pharmaceuticals and licensed to [[Company:Roche|Roche]] for clinical development, a novel nucleotide analog [[Chemistry:Prodrug|prodrug]] originally developed for the treatment of [[Medicine:Hepatitis C|hepatitis C]].<ref>{{cite journal | vauthors = Berliba E, Bogus M, Vanhoutte F, Berghmans PJ, Good SS, Moussa A, Pietropaolo K, Murphy RL, Zhou XJ, Sommadossi JP | display-authors = 6 | title = Safety, pharmacokinetics and antiviral activity of AT-527, a novel purine nucleotide prodrug, in HCV-infected subjects with and without cirrhosis | journal = Antimicrobial Agents and Chemotherapy | date = September 2019 | volume = 63 | issue = 12 | pmid = 31570394 | doi = 10.1128/AAC.01201-19 | pmc = 6879261 }}</ref><ref>{{cite journal | vauthors = Good SS, Moussa A, Zhou XJ, Pietropaolo K, Sommadossi JP | title = Preclinical evaluation of AT-527, a novel guanosine nucleotide prodrug with potent, pan-genotypic activity against hepatitis C virus | journal = PLOS ONE | year = 2020 | volume = 15 | issue = 1 | pages = e0227104 | pmid = 31914458 | doi = 10.1371/journal.pone.0227104 | pmc = 6949113 | bibcode = 2020PLoSO..1527104G | doi-access = free }}</ref> Bemnifosbuvir is the orally bioavailable hemisulfate salt of AT-511, which is metabolized in several steps to the active nucleotide triphosphate AT-9010, acting as an [[Biology:RNA polymerase|RNA polymerase]] inhibitor and thereby interfering with viral replication. Bemnifosbuvir has been researched for the treatment of [[Biology:Coronavirus|coronavirus]] diseases such as that produced by [[Biology:SARS-CoV-2|SARS-CoV-2]].<ref>{{cite journal | vauthors = Good SS, Westover J, Jung KH, Zhou XJ, Moussa A, La Colla P, Collu G, Canard B, Sommadossi JP | display-authors = 6 | title = AT-527, a Double Prodrug of a Guanosine Nucleotide Analog, Is a Potent Inhibitor of SARS-CoV-2 ''In Vitro'' and a Promising Oral Antiviral for Treatment of COVID-19 | journal = Antimicrobial Agents and Chemotherapy | volume = 65 | issue = 4 | date = March 2021 | pmid = 33558299 | doi = 10.1128/AAC.02479-20 | pmc = 8097421 }}</ref>  It showed good results in early [[Engineering:Clinical trial|clinical trial]]s but had inconsistent results at later stages, so the planned Phase 3 trials are being redesigned and results are not expected until late 2022.<ref>{{cite web | url = https://www.science.org/content/blog-post/527-fails | vauthors = Lowe D | title = AT-527 Fails a Phase II | work = In the Pipeline | publisher = Science.org | date = 19 October 2021 }}</ref><ref>{{cite web | url = https://www.biopharmadive.com/news/atea-roche-coronavirus-antiviral-drug-fails/608450/ | vauthors = Fidler B, Gardner J | title = Atea, Roche change plans for oral COVID-19 drug after trial setback. | work = Biopharmadive.com | date = 19 October 2021 }}</ref>{{update inline|date=August 2023}}

==See also==
* [[Chemistry:Galidesivir|Galidesivir]]
* [[Biology:Remdesivir|Remdesivir]]
* [[Chemistry:Lufotrelvir|Lufotrelvir]]
* [[Chemistry:Molnupiravir|Molnupiravir]]
* [[Chemistry:Sofosbuvir|Sofosbuvir]]

==References==
{{Reflist|35em}}

{{RNA antivirals}}

[[Category:Nucleotides]]
[[Category:Nitrogen heterocycles]]



{{Sourceattribution|Bemnifosbuvir}}