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

Table 2

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

No.	R^1	X	R^2	R^3	R^4	IC50/𝐾𝑖 (nM)	Kinase panel	In vivo	X-ray	Year/lit.
4	H	C	H	Me		α: 34^a	β + 24	Yes	—	2000, 2001, 2007 [32–34]
5	H	N	—			β: 25^b	β + 79	Yes	—	2004 [35]
6	H	N	—			β: 6^b	β + 79	Yes	—	2004 [35]
7	H	N	—			β: 4^a	—	—	—	2004 [36]
8	H	N	—			β: 26^a	β + 69	Yes	1Q3D^c	2004 [36]
9	H	C				β: 1.3^a	β + 36	Yes	—	2004 [37]
10	H	C				GSK-3: 2.0^a	GSK-3 + 3	Yes	—	2005 [38]
11	H	C				GSK-3: 0.7^a	GSK-3 + 3	Yes	—	2005 [38]
12	Br	C	H			β: 140^a	β + 5	Yes	1Q3D^c	2009 [39]
13	F	C	H	Me		β: 0.6^a	α & β + 315	Yes	1R0E	2010 [40]
14	H	C	H	H		β: 4470^a	—	—	—	2011 [41]
15	H	C	H	Me		β: 890^a	—	—	—	2011 [41]

^aIC₅₀ value; ^b𝐾_𝑖 value; ^cdocking studies, PDB code; α: GSK-3α; β: GSK-3β.