Journal Article

DZNE-2020-02370

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Inhibition of gamma-secretase by the CK1 inhibitor IC261 does not depend on CK1delta.

Höttecke, N. ; Liebeck, M. ; Baumann, K. ; Schubenel, R. ; Winkler, E.DZNE* ; Steiner, H.DZNE* ; Schmidt, B. (Corresponding author)

2010
Elsevier Science Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.bmcl.2010.02.110

Abstract: CK1 and gamma-secretase are interesting targets for therapeutic intervention in the treatment of cancer and Alzheimer's disease. The CK1 inhibitor IC261 was reported to inhibit gamma-secretase activity. The question is: Does CK1 inhibition directly influence gamma-secretase activity? Therefore we analyzed the SAR of 15 analogues and their impact on gamma-secretase activity. The most active compounds were investigated on CK1delta activity. These findings exclude a direct influence of CK1delta on gamma-secretase, because any change in the substitution pattern of IC261 diminished CK1 inhibition, whereas gamma-secretase inhibition is still exerted by several analogues.

Keyword(s): Amyloid Precursor Protein Secretases: antagonists & inhibitors (MeSH) ; Amyloid Precursor Protein Secretases: metabolism (MeSH) ; Binding Sites (MeSH) ; Casein Kinase I: antagonists & inhibitors (MeSH) ; Casein Kinase I: metabolism (MeSH) ; Casein Kinase Idelta: antagonists & inhibitors (MeSH) ; Casein Kinase Idelta: metabolism (MeSH) ; Indoles: chemistry (MeSH) ; Indoles: pharmacology (MeSH) ; Phloroglucinol: analogs & derivatives (MeSH) ; Phloroglucinol: chemistry (MeSH) ; Phloroglucinol: pharmacology (MeSH) ; Protease Inhibitors: chemistry (MeSH) ; Protease Inhibitors: pharmacology (MeSH) ; Structure-Activity Relationship (MeSH) ; IC 261 ; Indoles ; Protease Inhibitors ; Phloroglucinol ; Casein Kinase I ; Casein Kinase Idelta ; Amyloid Precursor Protein Secretases

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Contributing Institute(s):

1. Biochemistry of γ-Secretase (AG Steiner)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2010

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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