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

Table 6

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

No.	X	R^1	R^2	R^3	IC50 (nM)	Kinase panel	In vivo	X-ray	Year/lit.
37	N	OH	H	H	β: 22	β + 2	Yes	1Q41	2001, 2003, 2007 [31, 34, 58]
38	O	—	H	H	β: 600	β + 2	—	—	2001 [58]
39	N	OH	H	Br	α/β: 5	α/β + 19	Yes	1UV5 + 1Q41^a	2003, 2004 [63, 64]
40	N	OAc	H	Br	α/β: 10	α/β + 19	—	—	2003 [63]
41	O	—	H	Br	β: 45	β + 2	—	—	2004 [64]
42	N	OAc	Cl	Cl	β: 4	β + 2	—	—	2004 [64]
43	N	OAc	CH3	Br	β: 7	β + 2	—	—	2004 [64]
44	N		H	Br	α/β: 3.3	α/β + 2	Yes	1UV5^a	2008 [65]
45	N		H	Br	α/β: 5.0	α/β + 2	Yes	1UV5^a	2008 [65]
46	N		H	Br	α/β: 14	α/β + 2	Yes	—	2008 [65]
47	O	—	NH2	H	α/β: 80	α/β + 4	Yes	—	2009 [66]
48	O	—	NHAc	H	α/β: 7.5	α/β + 4	Yes	—	2009 [66]
49	N	OH	H	NO2	α/β: 40	α/β + 4	—	—	2009 [66]
50	N	OH	NO2	H	α/β: 2.1	α/β + 4	—	—	2009 [66]

^a Docking studies; PDB code; β: GSK-3β; α/β: GSK-3α/β.