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

Table 15

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

(a)

No.	R^1	R^2	IC50 (nM)	Kinase panel	In vivo	X-ray	Year/lit.
131	H		—	—	—	1I09^a	2007 [134]
132	H		β: 580	—	—	—	2007 [134]
133	H		β: 25	—	—	—	2007 [134]
134	Cl		β: 15	—	—	2O5K	2007 [134]
No.	R^3		𝐾𝑖 (nM)	Kinase panel	In vivo	X-ray	Year/lit.
135			β: 5800	β + 4	—	PDB n.d.^a	2008 [135]
136			β: 4100	β + 4	—	PDB n.d.^a	2008 [135]
137			β: 1500	β + 4	—	PDB n.d.^a	2008 [135]
No.		IC50 (nM)		Kinase panel	In vivo	X-ray	Year/lit.
138		—		—	Yes	—	2005 [136]

^aDocking studies, PDB code (n.d.: not denoted); β: GSK-3β.

(b)

No.	R^1	R^2	𝐾𝑖 (nM)	Kinase panel	In vivo	X-ray	Year/lit.
139	H		β: 1490	—	—	1Q3D^b	2010 [137]
140			β: 0.8	β + 13	—	—	2010 [137]
141			β: 2	β + 13	—	—	2010 [137]
142			β: <2	—	—	3L1S	2010 [137]
143			β: 4.5	β + 13	—	—	2010 [137]
No.		IC50 (nM)		Kinase panel	In vivo	X-ray	Year/lit.
144		α: 34		β + 39	Yes	1Q3D^b	2011 [138]
No.		R^3	IC50 (nM)	Kinase panel	In vivo	X-ray	Year/lit.
145			β: 4200	—	Yes	1Q4l^b	2009 [139]
146			β: 6400	—	—	—	2009 [139]
147		SCH2CH3	β: 7800	—	—	—	2009 [139]
No.		R^4	IC50 (nM)	Kinase panel	In vivo	X-ray	Year/lit.
148			β: 17.4	β + 2^a	Yes	—	2011 [140]
149			β: 8.5	β + 2^a	Yes	—	2011 [140]
150			β: 16.1	β + 2^a	Yes	—	2011 [140]

^aFurther, it was noted that the compound was screened against a broad panel of kinases; ^bdocking studies, PDB code; β: GSK-3β.

(c)

No.	Name	IC50 (nM)	Kinase panel	In vivo	X-ray	Year/lit.
151	Manzamine A	β: 10200	α and β + 4	Yes	—	2007 [141]
No.	Name	IC50 (nM)	Kinase panel	In vivo	X-ray	Year/lit.
152	Meridianin D	β: 2500	β + 5	Yes	—	2004 [142]
No.	Name	IC50 (nM)	Kinase panel	In vivo	X-ray	Year/lit.
153	Hymenialdisine	β: 10	β + 31	Yes	—	2000 [143]
No.	Name	IC50 (nM)	Kinase panel	In vivo	X-ray	Year/lit.
154	Dibromocantharelline	β: 3000	β + 3	—	1H8F^a	2010, 2011 [143, 144]

^aDocking studies, PDB code; β: GSK-3β.