Secutrelvir, also named as S-892216, is a reversible covalent 3CLpro inhibitor with highly potent antiviral activity and an EC50 value of 2.48 nM against SARS-CoV-2 infected cells. Structure-based design of a covalent modifier for compound 1 revealed that introducing a nitrile warhead increased 3CLpro inhibition activity by 180-fold. Subsequent optimization efforts yielded S-892216, which combined a favorable pharmacokinetic profile and high off-target selectivity. S-892216 exhibited antiviral activity against diverse SARS-CoV-2 variants, including major mutations reducing antiviral activities of nirmatrelvir and ensitrelvir. In SARS-CoV-2-infected mice, S-892216 inhibited viral replication in the lungs similar to ensitrelvir, although at a 30-fold lower dose.
MedKoo Cat#: 128532
Name: Secutrelvir
CAS#: 2996148-73-1
Chemical Formula: C23H16Cl2F3N5O2
Exact Mass: 521.0633
Molecular Weight: 522.31
Elemental Analysis: C, 52.89; H, 3.09; Cl, 13.57; F, 10.91; N, 13.41; O, 6.13
The following data is based on the product molecular weight 522.31 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
Unoh Y, Hirai K, Uehara S, Kawashima S, Nobori H, Sato J, Shibayama H, Hori A, Nakahara K, Kurahashi K, Takamatsu M, Yamamoto S, Zhang Q, Tanimura M, Dodo R, Maruyama Y, Sawa H, Watari R, Miyano T, Kato T, Sato T, Tachibana Y. Discovery of the Clinical Candidate S-892216: A Second-Generation of SARS-CoV-2 3CL Protease Inhibitor for Treating COVID-19. J Med Chem. 2025 Jul 5. doi: 10.1021/acs.jmedchem.5c00754. Epub ahead of print. PMID: 40616520.
