Table 1.

In vitro and in vivo parameters of M^pro inhibitors examined in the present study

		SARS- CoV2 RNA VeroE6 cell-based assay (µM)**		SARS- CoV2 Mpro enzyme assay (µM)*		T1/2# (h)	Cmax # (ng/mL)	Oral F# (%)
Compound	Structure	EC50	EC95	IC50	IC95
5h M.W. 575.6840		2.60 ± 0.50	9.47 ± 0.33	0.13 ± 0.11	1.5 ± 0.6	0.27§	n.d.	n.d.
TKB125 M.W. 593.6744		1.82 ± 0.96	8.39 ± 0.39	0.034 ± 0.006	1.02 ± 0.40	0.76 §	n.d.	n.d.
TKB198 M.W. 611.6648		0.27 ± 0.11	0.83 ± 0.03	0.023 ± 0.013	0.75 ± 0.27	0.83 §	85	1.98§
TKB245 M.W. 653.6936		0.03 ± 0.02	0.53 ± 0.33	0.007 ± 0.002	0.14 ± 0.07	3.82¶	1,901¶	48¶
TKB248 M.W. 669.7546		0.22 ± 0.08	0.87 ± 0.04	0.074 ± 0.034	6.00 ± 5.29	4.34¶	1,925¶	72¶
Nirmatrelvir M.W. 499.5352		0.94 ± 0.21	7.81 ± 1.55	0.013 ± 0.004	0.77 ± 0.25	1.03¶	1,157¶	56¶

Fifty % inhibitory concentration (IC₅₀) and 50% effective concentration (EC₅₀) values were calculated as previously published¹⁴. Data from three-four independent assays are shown as arithmetic means ± 1 S.D.

# Pharmacokinetic parameters were calculated using plasma concentration–time data and are shown as mean values.

§N = 2 to 3 male or female ICR mice.

¶N = 3 male PXB-mouse 10 mg/kg i.v. and p.o. (see Supplementary Fig. 2 for details). F is defined as the dose-normalized AUC after oral administration divided by the dose-normalized AUC after intravenous administration.

*Inhibition of SARS-CoV2 M^pro enzyme activity by compounds was measured with fluorescence resonance energy transfer (FRET) assay system.

**Cell-based anti-SARS-CoV2 activity by compounds was determined with RT-qPCR assays of viral RNA from SARS-CoV2-exposed VeroE6 cells. Source data are provided as a Source Data file.