Small-Molecule Inhibitors of GSK-3: Structural Insights and Their Application to Alzheimer's Disease Models

Table 3

Examples of bisindolyl maleimide and benzofuranyl-indolyl maleimide inhibitors with biological activity against GSK-3, selectivity, X-ray and reference.

No.

R^1

X

R^2

R^3

Y

Z

R^4

IC50/𝐾𝑖 (nM)

Kinase panel

In vivo

X-ray

Year/lit.

16

H

CH

Me

N

CH

H

β: 2.8^a

—

Yes

—

1999 [42]

17

H

N

N

N

H

β: 48^a

β + 54

Yes

—

2003 [43]

18

H

N

N

N

H

β: 34^a

β + 54

Yes

1H8F^c

2003 [43]

19

H

CH

N

CH

H

β: 25^a

β + 18

Yes

—

2003 [44]

20

H

CH

N

CH

H

β: 4^a

—

Yes

—

2003 [44]

21

H

N

N

N

H

β: 11^b

β + 65

Yes

—

2004 [45]

22

H

N

N

N

H

β: 36^b

β + 65

Yes

1H8F^c + 1AQ1^c

2004 [45]

23

H

CH

N

CH

H

β: 3^a

α & β + 98

—

2OW3

2007 [46]

24

5-Br

CH

Me

—

O

CH

H

β: 7.0^a (4.6^b)

β + 22

Yes

1Q3D^c

2007 [47]

25

5-F

CH

Me

—

O

CH

6-CH2OH

β: 0.35^a

β + 1

—

1R0E^c

2009 [48]

26

7-CH2OH

CH

Me

—

O

CH

H

β: 5.4^a

β + 1

—

1R0E^c

2009 [48]

27

7-CH2OMe

CH

Me

—

O

CH

H

β: 0.23^a

β + 1

Yes

—

2009 [48]

^a IC₅₀ value; ^b𝐾_𝑖 value; ^cDocking studies, PDB code; α: GSK-3α; β: GSK-3β.