IκB kinase ß (IKKß): Structure, transduction mechanism, biological function, and discovery of its inhibitors.
Int J Biol Sci
; 19(13): 4181-4203, 2023.
Article
in En
| MEDLINE
| ID: mdl-37705738
The effective approach to discover innovative drugs will ask natural products for answers because of their complex and changeable structures and multiple biological activities. Inhibitory kappa B kinase beta (IKKß), known as IKK2, is a key regulatory kinase responsible for the activation of NF-κB through its phosphorylation at Ser177 and Ser181 to promote the phosphorylation of inhibitors of kappa B (IκBs), triggering their ubiquitination and degradation to active the nuclear factor kappa-B (NF-κB) cascade. Chemical inhibition of IKKß or its genetic knockout has become an effective method to block NF-κB-mediated proliferation and migration of tumor cells and inflammatory response. In this review, we summarized the structural feature and transduction mechanism of IKKß and the discovery of inhibitors from natural resources (e.g. sesquiterpenoids, diterpenoids, triterpenoids, flavonoids, and alkaloids) and chemical synthesis (e.g. pyrimidines, pyridines, pyrazines, quinoxalines, thiophenes, and thiazolidines). In addition, the biosynthetic pathway of novel natural IKKß inhibitors and their biological potentials were discussed. This review will provide inspiration for the structural modification of IKKß inhibitors based on the skeleton of natural products or chemical synthesis and further phytochemistry investigations.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Biological Products
/
I-kappa B Kinase
Language:
En
Journal:
Int J Biol Sci
Journal subject:
BIOLOGIA
Year:
2023
Document type:
Article
Affiliation country:
China
Country of publication:
Australia