Table 1 In vitro and in vivo parameters of Mpro inhibitors examined in the present study

From: Identification of SARS-CoV-2 Mpro inhibitors containing P1’ 4-fluorobenzothiazole moiety highly active against SARS-CoV-2

  

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¶

  1. 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.
  2. # Pharmacokinetic parameters were calculated using plasma concentration–time data and are shown as mean values.
  3. §N = 2 to 3 male or female ICR mice.
  4. 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.
  5. *Inhibition of SARS-CoV2 Mpro enzyme activity by compounds was measured with fluorescence resonance energy transfer (FRET) assay system.
  6. **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.
Back to article page