Inhibition of γ-secretase by the CK1 inhibitor IC261 does not depend on CK1δ
Bioorg Med Chem Lett. 2010 Mar 4. [Epub ahead of print]
|Type of Publication:||Journal Article|
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 CK1δ on γ-secretase, because any change in the substitution pattern of IC261 diminished CK1 inhibition, whereas γ-secretase inhibition is still exerted by several analogues. Copyright © 2010 Elsevier Ltd. All rights reserved.