Table. 1 Enzymatic inhibitory activities, and preliminary evaluations of drug-like properties for representative tricyclic PLpro inhibitors and Jun12682

From: YL1004 is a SARS-CoV-2 papain-like protease inhibitor with immunomodulatory and antiviral activity in mice

Compound

R3

PLpro

IC50 (nM) a

VeroE6

CC50 (μM) a

CYP3A4 IC50 (μM) b

CYP2C9 IC50 (μM) b

P. O. 100 mg/kg AUC(0-t) (μg/L*h) b

Jun12682

-

32.1 ± 1.3

59.34 ± 2.32

-

-

73121

2i

18.4 ± 0.2

74.06 ± 11.32

1.87 ± 0.27

> 10

9291

4b

12.9 ± 0.2

38.99 ± 1.19

1.88 ± 0.02

1.67 ± 0.18

-

4e

15.3 ± 2.3

89.55 ± 1.26

2.15 ± 0.40

6.46 ± 0.46

31561

4k

13.7 ± 0.5

155.60 ± 0.96

6.29 ± 0.26

-

33503

4 l

26.1 ± 0.1

205.85 ± 0.49

> 10

-

381

6k

30.0 ± 2.2

91.56 ± 5.53

> 10

-

972

6 f (YL1004)

17.5 ± 0.6

226.90 ± 28.43

> 30

> 30

79818

6 g

20.5 ± 3.5

264.80 ± 17.25

> 10

-

15062

6 h

26.7 ± 0.8

62.02 ± 0.26

> 10

-

38395

6i

27.1 ± 3.0

70.05 ± 1.82

> 10

-

3765

  1. a IC50 values were determined by FRET enzymatic assay. Cytotoxicity CC50 was determined in Vero E6 cells with 72 h incubation. Data are presented as mean ± SD (n = 3 biological replicates); b “-” represents no data.
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