Modulating the interaction between CDK2 and cyclin A with a quinoline-based inhibitor.
Bioorg Med Chem Lett
; 24(1): 199-203, 2014 Jan 01.
Article
in En
| MEDLINE
| ID: mdl-24332088
ABSTRACT
A new class of quinoline-based kinase inhibitors has been discovered that both disrupt cyclin dependent 2 (CDK2) interaction with its cyclin A subunit and act as ATP competitive inhibitors. The key strategy for discovering this class of protein-protein disrupter compounds was to screen the monomer CDK2 in an affinity-selection/mass spectrometry-based technique and to perform secondary assays that identified compounds that bound only to the inactive CDK2 monomer and not the active CDK2/cyclin A heterodimer. Through a series of chemical modifications the affinity (Kd) of the original hit improved from 1 to 0.005µM.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Quinolines
/
Cyclin A
/
Protein Kinase Inhibitors
/
Cyclin-Dependent Kinase 2
Limits:
Humans
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2014
Document type:
Article