Ziresovir

• CAT Number: I005987
• CAS Number: 1422500-60-4
• PubChem Substance ID: 71262247
• Molecular Formula: C22H25N5O3S
• Molecular Weight: 439.5
• Purity: 98%
• Synonyms: AK0529; RO-0529; RO0529
• Target: RSV F
• Appearance: White to off-white (Solid)
• Analysis method: HPLC
• IUPAC Name: N-[(3-aminooxetan-3-yl)methyl]-2-(1,1-dioxo-3,5-dihydro-2H-1λ6,4-benzothiazepin-4-yl)-6-methylquinazolin-4-amine
• InChI: InChI=1S/C22H25N5O3S/c1-15-6-7-18-17(10-15)20(24-12-22(23)13-30-14-22)26-21(25-18)27-8-9-31(28,29)19-5-3-2-4-16(19)11-27/h2-7,10H,8-9,11-14,23H2,1H3,(H,24,25,26)
• InChIKey: GAAICKUTDBZCMT-UHFFFAOYSA-N
• SMILES: CC1=CC2=C(C=C1)N=C(N=C2NCC3(COC3)N)N4CCS(=O)(=O)C5=CC=CC=C5C4

Ziresovir(CAT: I005987), also known as RO-0529 and AK0529, is a promising inhibitor of the respiratory syncytial virus (RSV) fusion (F) protein. It is currently undergoing phase 2 clinical trials for the treatment of RSV infections. RO-0529 has shown potent antiviral activity, with single-digit nanomolar (nM) EC50 potency against both laboratory strains and clinical isolates of RSV in cellular assays. In preclinical studies using a BALB/c mouse model of RSV viral infection, RO-0529 demonstrated a viral load reduction of more than one log. The specificity of RO-0529 as an RSV F protein inhibitor has been confirmed through the identification of drug-resistant mutations (D486N, D489V, and D489Y) in the RSV F protein. Furthermore, RO-0529 inhibits RSV F protein-induced cell-cell fusion in cellular assays.

Reference

1. J Med Chem. 2019 Jul 11;62(13):6003-6014. doi: 10.1021/acs.jmedchem.9b00654. Epub
2019 Jun 26.

Discovery of Ziresovir as a Potent, Selective, and Orally Bioavailable
Respiratory Syncytial Virus Fusion Protein Inhibitor.

Zheng X(1), Gao L(1), Wang L(1), Liang C(1), Wang B(1), Liu Y(1), Feng S(1),
Zhang B(1), Zhou M(1), Yu X(1), Xiang K(1), Chen L(1), Guo T(2), Shen HC(1), Zou
G(3), Wu JZ(3), Yun H(1).

Author information:
(1)Roche Pharma Research and Early Development , Roche Innovation Center Shanghai
, Building 5, 720 Cailun Road , Shanghai 201203 , China.
(2)International Discovery Service Unit, Research Service Division , WuXi AppTec
(Shanghai) Co., Ltd. , Lane 31, Yiwei Road, Waigaoqiao , Shanghai , 200131 ,
China.
(3)Ark Biosciences Inc. , 780 Cailun Road, Suite 701, ZhangJiang Hitech Park,
Pudong , Shanghai 201203 , China.

Ziresovir (RO-0529, AK0529) is reported here for the first time as a promising
respiratory syncytial virus (RSV) fusion (F) protein inhibitor that currently is
in phase 2 clinical trials. This article describes the process of RO-0529 as a
potent, selective, and orally bioavailable RSV F protein inhibitor and highlights
the in vitro and in vivo anti-RSV activities and pharmacokinetics in animal
species. RO-0529 demonstrates single-digit nM EC50 potency against laboratory
strains, as well as clinical isolates of RSV in cellular assays, and more than
one log viral load reduction in BALB/c mouse model of RSV viral infection.
RO-0529 was proven to be a specific RSV F protein inhibitor by identification of
drug resistant mutations of D486N, D489V, and D489Y in RSV F protein and the
inhibition of RSV F protein-induced cell-cell fusion in cellular assays.