Table 4 Comparison of PARP1 selective inhibitors and selected first-generation PARP inhibitors

PARP1 IC₅₀ (μM)^a

0.007

0.009

<0.01

0.003

<0.005

PARP2 IC₅₀ (μM)^a

0.006

0.030

0.691

>1.4

>93

PARP1/2 selectivity fold

1

3

>200

>460

19107

PARP3/5a/6 IC₅₀ (μM)^a

0.2/70/1.8

0.2/1.9.1.1

0.5/>10/not reported

3.4/ > 89/26

All > 100

PARP1 trapping^b

+

++

-

++

Yes

PARP2 trapping^b

+

++

-

-

-

DLD1 BRCA2^−/− cell line antiprolifertive GI₅₀ (nM)

11

0.5

Not reported

0.4

1.4

Pgp substrate

Yes

Yes

No

Yes

No

CNS penetration

Limited, Rat/Monkey Kpuu: <0.03/<0.1

Limited, Rat Kpuu: <0.03

Yes, with a brain/plasma ratio of 4-10 in rats and mouse

Limited, Rat/Monkey Kpuu: <0.05/<0.01

Yes, with Rat Kpuu 0.31