Danoprevir

Danoprevir
Clinical data
Other namesITMN-191, RG-7227
ATC code
  • None
Legal status
Legal status
  • Investigational
Identifiers
IUPAC name
  • (2R,6S,12Z,13aS,14aR,16aS)-6-[(tert-Butoxycarbonyl)amino]-14a-[N-(cyclopropanesulfonyl)carbamoyl]-5,16-dioxo- 1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a] [1,4]diazacyclopentadecin-2-yl 4-fluoro-1,3-dihydro-2H-isoindole-2-carboxylate
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
NIAID ChemDB
PDB ligand
Chemical and physical data
FormulaC35H46FN5O9S
Molar mass731.84 g·mol−1
3D model (JSmol)
    SMILES
    • CC(C)(C)OC(=O)N[C@@H]1CCCCC\C=C/[C@@H]2C[C@]2(NC(=O)[C@@H]3C[C@H](CN3C1=O)OC(=O)N4Cc5cccc(F)c5C4)C(=O)NS(=O)(=O)C6CC6
    InChI
    • InChI=1S/C35H46FN5O9S/c1-34(2,3)50-32(45)37-27-13-8-6-4-5-7-11-22-17-35(22,31(44)39-51(47,48)24-14-15-24)38-29(42)28-16-23(19-41(28)30(27)43)49-33(46)40-18-21-10-9-12-26(36)25(21)20-40/h7,9-12,22-24,27-28H,4-6,8,13-20H2,1-3H3,(H,37,45)(H,38,42)(H,39,44)/b11-7-/t22-,23-,27-,28+,35-/m1/s1
    • Key:ZVTDLPBHTSMEJZ-UPZRXNBOSA-N

    Danoprevir (INN)[1] is an orally available[2] 15-membered macrocyclic peptidomimetic inhibitor of NS3/4A HCV protease.[3] It contains acylsulfonamide, fluoroisoindole and tert-butyl carbamate moieties. Danoprevir is a clinical candidate based on its favorable potency profile against multiple HCV genotypes 1–6 and key mutants (GT1b, IC50 = 0.2–0.4 nM; replicon GT1b, EC50 = 1.6 nM).[4] Danoprevir has been evaluated in an open-label, single arm clinical trial in combination with ritonavir for treating COVID-19[5] and favourably compared to lopinavir/ritonavir in a second trial.[6]

    History

    Danaoprevir was initially developed by Array BioPharma then licensed to Roche for further development and commercialization. In 2013, Danoprevir was licensed to Ascletis by Roche for development and production in China under the tradename Ganovo.[7][8]

    References

    1. ↑ "International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 64" (PDF). World Health Organization. p. 265. Retrieved 25 February 2017.
    2. ↑ Deutsch M, Papatheodoridis GV (August 2010). "Danoprevir, a small-molecule NS3/4A protease inhibitor for the potential oral treatment of HCV infection". Current Opinion in Investigational Drugs. 11 (8): 951–63. PMID 20721837.
    3. ↑ Jiang Y, Andrews SW, Condroski KR, Buckman B, Serebryany V, Wenglowsky S, et al. (March 2014). "Discovery of danoprevir (ITMN-191/R7227), a highly selective and potent inhibitor of hepatitis C virus (HCV) NS3/4A protease". Journal of Medicinal Chemistry. 57 (5): 1753–69. doi:10.1021/jm400164c. PMID 23672640.
    4. ↑ Levin J, ed. (2015). "7.4.1 Danoprevir (ITMN-191)". Macrocycles in Drug Discovery. Drug Discovery. The Royal Society of Chemistry. doi:10.1039/9781782623113. ISBN 978-1-84973-701-2.
    5. ↑ Chen H, Zhang Z, Wang L, Huang Z, Gong F, Li X; et al. (2020). "First clinical study using HCV protease inhibitor danoprevir to treat COVID-19 patients". Medicine (Baltimore). 99 (48): e23357. doi:10.1097/MD.0000000000023357. PMC 7710192. PMID 33235105.{{cite journal}}: CS1 maint: multiple names: authors list (link)
    6. ↑ Zhang Z, Wang S, Tu X, Peng X, Huang Y, Wang L; et al. (2020). "A comparative study on the time to achieve negative nucleic acid testing and hospital stays between danoprevir and lopinavir/ritonavir in the treatment of patients with COVID-19". J Med Virol. 92 (11): 2631–2636. doi:10.1002/jmv.26141. PMC 7300667. PMID 32501538.{{cite journal}}: CS1 maint: multiple names: authors list (link)
    7. ↑ Ng E (17 July 2018). "Singapore sovereign wealth fund GIC to invest US$75 million in Chinese drug maker Ascletis' Hong Kong IPO". South China Morning Post. Retrieved 10 Aug 2018.
    8. ↑ Speights K (21 February 2017). "How High Can Array BioPharma Inc. Stock Go?". The Motley Fool. Retrieved 13 August 2018.

    Further reading

    Seiwert SD, Andrews SW, Jiang Y, Serebryany V, Tan H, Kossen K, et al. (December 2008). "Preclinical characteristics of the hepatitis C virus NS3/4A protease inhibitor ITMN-191 (R7227)". Antimicrobial Agents and Chemotherapy. 52 (12): 4432–41. doi:10.1128/AAC.00699-08. PMC 2592891. PMID 18824605.


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