Home
Resources
Publications
Chemical Control of Mammalian Circadian Behavior Through Dual Inhibition of Casein Kinase Iα and δ

Chemical Control of Mammalian Circadian Behavior Through Dual Inhibition of Casein Kinase Iα and δ

Jae Wook Lee, Tsuyoshi Hirota, Daisuke Ono, Sato Honma, Ken-Ichi Honma, Keunwan Park, Steve A Kay

J Med Chem. 2019 Feb 28;62(4):1989-1998.

PMID: 30707835

Abstract:

Circadian rhythms are controlled by transcriptional feedback loops of clock genes and proteins. The stability of clock proteins is regulated by post-translational modification, such as phosphorylation by kinases. In particular, casein kinase I (CKI) phosphorylates the PER protein to regulate proteasomal degradation and nuclear localization. Therefore, CKI inhibition can modulate mammalian circadian rhythms. In the present study, we have developed novel CKIα and CKIδ dual inhibitors by extensive structural modification of N9 and C2 position of longdaysin. We identified NCC007 that showed stronger period effects (0.32 μM for 5 h period lengthening) in a cell-based circadian assay. The following in vitro kinase assay showed that NCC007 inhibited CKIα and CKIδ with an IC50 of 1.8 and 3.6 μM. We further demonstrated that NCC007 lengthened the period of mouse behavioral rhythms in vivo. Thus, NCC007 is a valuable tool compound to control circadian rhythms through CKI inhibition.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42415291	Longdaysin			Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: