High-throughput screening identified the imidazo[1,2-a]pyridine and bisanilinopyrimidine series as inhibitors of the cyclin-dependent kinase CDK4. Comparison of their experimentally-determined binding modes and emerging structure-activity trends led to the development of potent and selective imidazo[1,2-a]pyridine inhibitors for CDK4 and in particular CDK2.

Calmodulin plays a vital role in mediating bidirectional synaptic plasticity by activating either calcium/calmodulin-dependent protein kinase II (CaMKII) or protein phosphatase 2B (PP2B) at different calcium concentrations. We propose an allosteric model for calmodulin activation, in which binding to calcium facilitates the transition between a low-affinity [tense (T)] and a high-affinity [rela...

As its name implies, calcium/calmodulin-dependent protein kinase II (CaMKII) is calcium dependent. In its basal state, the activity of CaMKII is extremely low. Regulation of intracellular calcium levels allows the neuron to link activity with phosphorylation by CaMKII. This review will briefly summarize our current understanding of the intramolecular mechanisms of activity regulation and their ...