Protein kinases are attractive therapeutic targets because their dysregulation underlies many diseases, including cancer. The high conservation of the kinase domain and the evolution of drug resistance, however, pose major challenges to the development of specific kinase inhibitors. We recently discovered selective Src kinase inhibitors from a DNA-templated macrocycle library. Here, we reveal t...

Quantitative relationships between molecular structure and p56(lck) protein tyrosine kinase inhibitory activity of 50 flavonoid derivatives are discovered by MLR and GA-PLS methods. Different QSAR models revealed that substituent electronic descriptors (SED) parameters have significant impact on protein tyrosine kinase inhibitory activity of the compounds. Between the two statistical methods em...

Necroptosis, as a novel concept, has been recently introduced in scientific literature. Much of our knowledge about necroptosis comes from ligation of tumor necrosis factor-α to its receptor, TNF receptor 1. Receptor-interacting protein kinase 1, receptor-interacting protein kinase 3 and its substrate, the pseudokinase mixed lineage kinase domain-like protein, have been comprehensively st...

diabetic retinopathy is the lead among causes of blindness in north america. glucose-induced endothelial injury is the most important cause of diabetic retinopathy and other vascular complications. extracellular signal-regulated kinase 5 (erk5), also known as big mitogen-activated protein kinase 1 (bmk1), is a member of mitogen-activated protein kinases (mapk) family. physiologically, it is cri...

Because dysregulation and mutations of protein kinases play causal roles in human disease, this family of enzymes has become one of the most important drug targets over the past two decades. The X-ray crystal structures of 21 of the 27 FDA-approved small molecule inhibitors bound to their target protein kinases are depicted in this paper. The structure of the enzyme-bound antagonist complex is ...

Phosphatidylinositol 3-kinase (PI 3-kinase) and protein kinase B are critical players in cell proliferation and survival. Their downstream effector protein kinase, p70 S6 kinase, has an established role in protein translation. The mechanism by which bacterial LPS induces production of nitric oxide (NO) in murine macrophages is incompletely understood, and a role for PI 3-kinase/p70 S6 kinase pa...

Objective: Cancer is the major cause of mortality in most developing countries. Enormous chemotherapeutic agents developed are still need improvements survival rates and quality life for cancer patients. Pro-viral Integration site Moloney murine leukemia virus (PIM1) a family serine/threonine kinase, regulated by calcium/calmudulin have been identified as unique molecular target oncogenesis. PI...

Protein kinases are critical drug targets for treating a large variety of human diseases. Type-III kinase inhibitors have attracted increasing attention as highly selective therapeutics. Thus, understanding the binding mechanism of existing type-III kinase inhibitors provides useful insights into designing new type-III kinase inhibitors. In this work, we have systematically studied the binding ...

Acrosome reaction (AR) is an exocytotic process of fundamental importance for the spermatozoon to fertilize the oocyte. The mechanisms mediating this process are only partially defined. The aim of the present study was to investigate the role of various kinases and the extracellular signal-regulated kinase (ERK) pathway in the induction of the AR and associated phosphorylation of tyrosine (Tyr)...