| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1374303 | Bioorganic & Medicinal Chemistry Letters | 2010 | 6 Pages |
CK1 and γ-secretase are interesting targets for therapeutic intervention in the treatment of cancer and Alzheimer’s disease. The CK1 inhibitor IC261 was reported to inhibit γ-secretase activity. The question is: Does CK1 inhibition directly influence γ-secretase activity? Therefore we analyzed the SAR of 15 analogues and their impact on γ-secretase activity. The most active compounds were investigated on CK1δ activity. These findings exclude a direct influence of CK1δon γ-secretase, because any change in the substitution pattern of IC261 diminished CK1 inhibition, whereas γ-secretase inhibition is still exerted by several analogues.
Graphical abstractStructural similarity of IC261 and the GSM of the Sulindac-series (2, 4).Figure optionsDownload full-size imageDownload as PowerPoint slide
