Review Article
Small-Molecule Inhibitors of GSK-3: Structural Insights and Their Application to Alzheimer's Disease Models
Table 9
Examples of pyrimidine inhibitors with biological activity against GSK-3, selectivity, X-ray, and reference.
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| No. | R1 | R2 | R3 | R4 | IC50/ (nM) | Kinase panel | In vivo | X-ray | Year/lit. |
| 79 | | | H | β: 2.5a | — | Yes | — | 2004 [91] | 80 | | | H | β: 100a | — | Yes | 1GNGc | 2001; and 2004 [28, 91] | 81 | | | H | β: 4.0a | — | Yes | 1GNGc | 2001; and 2004 [28, 91] | 82 | | H | | β: 2400a | — | — | — | 2008 [92] | 83 | | H | | β: 1700a | — | — | — | 2008 [92] | 84 | | H | | α: 1020a β: 960a | — | — | — | 2008 [92] | 85 | | H | | α: 1900a β: 760a | — | — | — | 2008 [92] | 86 | | H | | α: 350a β: 180a | — | — | — | 2008 [92] | 87 | | H | | α: 6700a β: 3500a | — | — | — | 2008 [92] | 88 | | NO2 | H | | α: 270a β: 150a | — | — | — | 2008 [92] | 89 | | CF3 | H | | α: 750a β: 490a | — | — | — | 2008 [92] | 90 | | H | | α: 330a β: 628a | α and β + 1 | — | 1Q5Kc | 2008 [92] | 91 | | NO2 | H | | α: 74a β: 92a | α and β + 1 | — | — | 2008 [92] | 92 | | H | | α: 9a β: 13a | α and β + 1 | — | — | 2008 [92] | 93 | | CF3 | H | | α: 61a β: 41a | α and β + 1 | Yes | — | 2008 [92] | 94 | H | Me | | | GSK-3: 7b | GSK-3 + 4 | — | 3I4B | 2009 [93] | 95 | | | H | | α: 10 β: 6.7a (9.8b) | α and β + 20 | Yes | — | 2003, and 2007 [34, 94] | 96 | | | H | | α: 0.65 β: 0.58a (0.87b) | α and β + 20 | Yes | — | 2003, and 2007 [34, 94] |
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a IC50 value; b value; cdocking studies, PDB code (n.d.: not denoted); α: GSK-3α; β: GSK-3β.
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