Emerging drug profile: cyclin-dependent kinase inhibitors

Cyclin-Dependent Kinase Inhibitors as Anticancer Therapeutics.

Cyclin-dependent kinases (CDKs) have been considered promising drug targets for a number of years, but most CDK inhibitors have failed rigorous clinical testing. Recent studies demonstrating clear anticancer efficacy and reduced toxicity of CDK4/6 inhibitors such as palbociclib and multi-CDK inhibitors such as dinaciclib have rejuvenated the field. Favorable results with palbociclib and its rec...

3D-QSAR and docking analysis on a series of multi-cyclin-dependent kinase inhibitors using CoMFA, and CoMSIA

A series of 42 Pyrazolo[4,3-h]quinazoline-3-carboxamides as multi-cyclin-dependent kinaseinhibitors regarded as promising antitumor agents to complement the existing therapies, wassubjected to a three-dimensional quantitative activity relationship (3D QSAR). Different QSARmethods, comparative molecular field analysis (CoMFA), CoMFA region focusing, andcomparative molecular similarity indices an...

Cyclin-dependent kinase inhibitors sensitize tumor cells to nutlin-induced apoptosis: a potent drug combination.

Current chemotherapy focuses on the use of genotoxic drugs that may induce general DNA damage in cancer cells but also high levels of toxicity in normal tissues. Nongenotoxic activation of p53 by targeting specific molecular pathways therefore provides an attractive therapeutic strategy in cancers with wild-type p53. Here, we explored the antitumor potential of cyclin-dependent kinase (CDK) inh...

Functional analysis of cyclin-dependent kinase inhibitors of Arabidopsis.

Cyclin-dependent kinase inhibitors, such as the mammalian p27(Kip1) protein, regulate correct cell cycle progression and the integration of developmental signals with the core cell cycle machinery. These inhibitors have been described in plants, but their function remains unresolved. We have isolated seven genes from Arabidopsis that encode proteins with distant sequence homology with p27(Kip1)...

Leukocyte Adhesion and Migration Cyclin-Dependent Kinase Inhibitors Block