Background: Mammalian cell division is regulated by a complex includes cyclin-dependent kinases (Cdks) and cyclins, Cdk/cyclin complex. The activity of the complex is regulated by Cdk inhibitors (CKIs) compressing CDK4 (INK4) and CDK-interacting protein/kinase inhibitory protein (CIP/KIP) family. Hypermethylation of CKIs has been reported in various cancers. DNA methyltransferase inhibitors (DN...

Modulation of protein kinase FA/glycogen synthase kinase-3alpha (kinase FA/GSK-3alpha) by reversible tyrosine phosphorylation/dephosphorylation was investigated. In addition to genistein, other protein tyrosine kinase (PTK) inhibitors, such as tyrphostin A47 and B42, also could induce tyrosine dephosphorylation and inactivation of kinase FA/GSK-3alpha in A431 cells, and this process was found t...

Various protein kinases including kinase A (PKA), Ca2+-calmodulin (CaMK), phosphoinositide 3-kinase (PI3K), C (PKC) and mitogen-activated (MAPK: ERK1/2, p38-MAPK JNK) are integral part of different signal transduction pathways, which known to regulate cardiac structure, function metabolism. In addition, these transducing proteins involved in the regulation cation transport, cellular growth, gen...

Protein kinase CK1? expression and activity is involved in different pathological situations that include neuroinflammatory neurodegenerative diseases. For this reason, protein has become a possible therapeutic target for these conditions. 5,6-fused bicyclic heteroaromatic systems resemble adenine of ATP represent optimal scaffolds the development new class competitive inhibitors. In particular...

The cellular effects of stromal cell-derived factor-1 (SDF-1) are mediated primarily by binding to the CXC chemokine receptor-4. We report in this study that SDF-1 and its peptide analogues induce a concentration- and time-dependent accumulation of phosphatidylinositol-(3,4,5)-trisphosphate (PtdIns(3,4,5)P3) in Jurkat cells. This SDF-1-stimulated generation of D-3 phosphoinositide lipids was in...

Design of irreversible inhibitors is an emerging and relatively less explored strategy for the design of protein kinase inhibitors. In this paper, we present a computational workflow that was specifically conceived to assist such design. The workflow takes the form of a multi-step procedure that includes: the creation of a database of already known reversible inhibitors of protein kinases, the ...

There is extensive evidence from the molecular and genomic analysis of human cancers that the PI 3-kinase (phosphoinositide 3-kinase)-Akt/PKB (protein kinase B) pathway is deregulated in malignant progression. Furthermore, the causal involvement of PI 3-kinase is supported by gene-knockout mouse models. Prototype inhibitors show evidence of anticancer activity in vitro and in vivo animal models...