Download MendeleyModulating the interaction between CDK2 and cyclin A with a quinoline-based inhibitor.
Deng, Y., Shipps, G.W., Zhao, L., Siddiqui, M.A., Popovici-Muller, J., Curran, P.J., Duca, J.S., Hruza, A.W., Fischmann, T.O., Madison, V.S., Zhang, R., McNemar, C.W., Mayhood, T.W., Syto, R., Annis, A., Kirschmeier, P., Lees, E.M., Parry, D.A., Windsor, W.T.(2014) Bioorg Med Chem Lett 24: 199-203
- PubMed: 24332088
- DOI: https://doi.org/10.1016/j.bmcl.2013.11.041
- Primary Citation of Related Structures:
4NJ3 - PubMed 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.
Organizational Affiliation:
Merck Research Laboratories, 320 Bent Street, Cambridge, MA 02141, USA. Electronic address: yongqi.deng@merck.com.
