Table 2 Biological activity and selectivity of PARP1-selective molecules generated by CMD-GEN

From: A structure-based framework for selective inhibitor design and optimization

Entry

Structure

PARP1 Enzyme

PARP2 Enzyme

Selectivity PARP-2/1

% control

@ 0.01 μMa

% control

@ 10 μMa

IC50 (nM)b

% control

@ 0.01 μMa

% control

@ 1 μMa

IC50 (nM)b

Z2*

29.6

99.2

20.9

3.9

100.3

282.1

13.49

Z5

7.3

12.7

>10000

−0.8

1.1

>10000

 

Z6*

16.3

62.8

6789

6.5

2.0

>10000

>1.47

Y1*

28.1

97.7

42.6

3.6

2.8

>10000

>234.74

Y2

−0.1

47.4

9800

2.3

−1.8

>10000

>1.02

Y4

20.7

99.0

86.5

−1.6

99.0

741.4

8.57

Y5

46.0

98.8

12.7

1.4

16.4

>10000

>787.4

Y6

70.5

99.1

6.0

87.6

101.3

2.4

0.4

Olaparib

   

0.7

  

1.4

 
  1. a% control, The inhibitory activity was evaluated at the compound.
  2. bIC50, compound’s concentration required to inhibit PARP1/2 enzyme activity by 50%; To improve practical synthetic accessibility, some selected molecules were structurally simplified and annotated with * (Fig. S10).
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