YH-53

YH-53 is a potent 3CLpro inhibitor with Ki values of 6.3 nM, 34.7 nM for SARS-CoV-1 3CLpro and SARS-CoV-2 3CLpro, respectively. YH-53 strongly blocks the SARS-CoV-2 replication. YH-53 is a peptidomimetic compound with a unique benzothiazolyl ketone. YH-53 has the potential for COVID-19 research[1][2].

YH-53 (1-25 μM; for 24 h) efficiently reduces copies of total RNA with increased concentrations in VeroE6/TMPRSS2 cells[1]. YH-53 (1, 5, 10, 15, 20, 25 μM; for 48 h) with 10 μM completely blocks the viral proliferation against SARS-CoV-2 were examined by a cytopathic effect (CPE) assay in Vero cells[1]. YH-53 (10, 100 μM; for 24 h) has no cytotoxicity with a CC50 value of >100 μM in vero cells[1]. YH-53 (10 μM) moderately inhibits CYP1A2, CYP2D6, and CYP2C8 (26.6%, 38.0%, 66.4%, respectively). YH-53 has no inhibition on CYP2C9 and CYP3A4[1]. YH-53 inhibits SARS-CoV 3CLpro with an IC50 of 0.74 μM.

YH-53 (0.1 mg/kg; iv) has a T1/2 of 2.97 hours, an AUC0-∞ of 19.7 ng•h/mL, a Vd of 3.51 L/kg in rats[1]. YH-53 (0.5 mg/kg; oral) has a T1/2 of 9.64 hours, an AUC0-∞ of 3.49 ng•h/mL, a Cmax of 1.08 ng/mL in rats[1].

[1]. Sho Konno, et al. 3CL Protease Inhibitors with an Electrophilic Arylketone Moiety as Anti-SARS-CoV-2 Agents. J Med Chem. 2021 Jul27;acs.jmedchem.1c00665.
[2]. Pillaiyar Thanigaimalai, et al. Development of potent dipeptide-type SARS-CoV 3CL protease inhibitors with novel P3 scaffolds: design, synthesis, biological evaluation, and docking studies. Eur J Med Chem. 2013 Oct;68:372-84.