AT-527

  • CAT Number: I022587
  • CAS Number: 2241337-84-6
  • Molecular Formula: C48H68F2N14O18P2S
  • Molecular Weight: 1261.1563
  • Purity: 98%
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AT-527, a hemisulfate salt of AT-511, a guanosine nucleotide prodrug, is a potent and orally active HCV viral replication inhibitor. AT-511 is a prodrug form of the antiviral nucleoside analog AT-9010. It reduces the infectious virus yield in cells infected with Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome CoV (SARS-CoV), SARS-CoV-2, human CoV 229E (HCoV-229E), and HCoV-OC43 (EC90s = 37, 0.47, 2.8, 1.2, and 0.5 µM, respectively).

Catalog Number I022587
CAS Number 2241337-84-6
Synonyms

AT 527; AT-527; AT527; RG 6422; RG-6422; RG6422

Molecular Formula

C48H68F2N14O18P2S

Purity 98
Solubility To be determined
Storage Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
IUPAC Name isopropyl ((S)-(((2R,3R,4R,5R)-5-(2-amino-6-(methylamino)-9H-purin-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)-L-alaninate hemisulfate
InChI InChI=1S/2C24H33FN7O7P.H2O4S/c2*1-13(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;1-5(2,3)4/h2*6-10,12-14,16,18,22,33H,11H2,1-5H3,(H,31,35)(H3,26,27,29,30);(H2,1,2,3,4)/t2*14-,16+,18+,22+,24+,40-;/m00./s1
InChIKey QIGYBLSWYRTXCA-NVSCJZCKSA-N
SMILES C[C@@H](C(OC(C)C)=O)N[P@@](OC1=CC=CC=C1)(OC[C@H]2O[C@@H](N3C=NC4=C(NC)N=C(N)N=C34)[C@](C)(F)[C@@H]2O)=O.C[C@@H](C(OC(C)C)=O)N[P@@](OC5=CC=CC=C5)(OC[C@H]6O[C@@H](N7C=NC8=C(NC)N=C(N)N=C78)[C@](C)(F)[C@@H]6O)=O.O=S(O)(O)=O
Reference

1: Yavuz S, Komsuoğlu Çelikyurt FI. Antiviral treatment of COVID-19: An update. Turk J Med Sci. 2021 Aug 15. doi: 10.3906/sag-2106-250. Epub ahead of print. PMID: 34391321.
2: Wang X, Sacramento CQ, Jockusch S, Chaves OA, Tao C, Fintelman-Rodrigues N, Chien M, Temerozo JR, Li X, Kumar S, Xie W, Patel DJ, Meyer C, Garzia A, Tuschl T, Bozza PT, Russo JJ, Souza TML, Ju J. Combination of Antiviral Drugs to Inhibit SARS-CoV-2 Polymerase and Exonuclease as Potential COVID-19 Therapeutics. bioRxiv [Preprint]. 2021 Jul 21:2021.07.21.453274. doi: 10.1101/2021.07.21.453274. PMID: 34312622; PMCID: PMC8312893.
3: Do TND, Donckers K, Vangeel L, Chatterjee AK, Gallay PA, Bobardt MD, Bilello JP, Cihlar T, De Jonghe S, Neyts J, Jochmans D. A robust SARS-CoV-2 replication model in primary human epithelial cells at the air liquid interface to assess antiviral agents. Antiviral Res. 2021 Aug;192:105122. doi: 10.1016/j.antiviral.2021.105122. Epub 2021 Jun 26. PMID: 34186107; PMCID: PMC8233549.
4: Good SS, Westover J, Jung KH, Zhou XJ, Moussa A, La Colla P, Collu G, Canard B, Sommadossi JP. 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. Antimicrob Agents Chemother. 2021 Mar 18;65(4):e02479-20. doi: 10.1128/AAC.02479-20. PMID: 33558299; PMCID: PMC8097421.
5: Cusack DA. COVID-19 pandemic: Coroner’s database of death inquiries with clinical epidemiology and total and excess mortality analyses in the District of Kildare March to June 2020. J Forensic Leg Med. 2020 Nov;76:102072. doi: 10.1016/j.jflm.2020.102072. Epub 2020 Oct 31. PMID: 33157341; PMCID: PMC7604184.
6: Good SS, Moussa A, Zhou XJ, Pietropaolo K, Sommadossi JP. Preclinical evaluation of AT-527, a novel guanosine nucleotide prodrug with potent, pan- genotypic activity against hepatitis C virus. PLoS One. 2020 Jan 8;15(1):e0227104. doi: 10.1371/journal.pone.0227104. PMID: 31914458; PMCID: PMC6949113.
7: Berliba E, Bogus M, Vanhoutte F, Berghmans PJ, Good SS, Moussa A, Pietropaolo K, Murphy RL, Zhou XJ, Sommadossi JP. Safety, pharmacokinetics and antiviral activity of AT-527, a novel purine nucleotide prodrug, in HCV-infected subjects with and without cirrhosis. Antimicrob Agents Chemother. 2019 Sep 30;63(12):e01201-19. doi: 10.1128/AAC.01201-19. Epub ahead of print. PMID: 31570394; PMCID: PMC6879261.
8: Cauci S, Di Santolo M, Casabellata G, Ryckman K, Williams SM, Guaschino S. Association of interleukin-1beta and interleukin-1 receptor antagonist polymorphisms with bacterial vaginosis in non-pregnant Italian women. Mol Hum Reprod. 2007 Apr;13(4):243-50. doi: 10.1093/molehr/gam002. Epub 2007 Feb 21. PMID: 17314118.
9: Mobley PW, Waring AJ, Sherman MA, Gordon LM. Membrane interactions of the synthetic N-terminal peptide of HIV-1 gp41 and its structural analogs. Biochim Biophys Acta. 1999 Apr 14;1418(1):1-18. doi: 10.1016/s0005-2736(99)00014-0. PMID: 10209206.

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