New Trends in Pharmacology & Drug Development

Aurora kinases control multiple events during cell cycle progression and are essential for mitotic and meiotic bipolar spindle assembly and function. There are three aurora kinases in mammals, some of which have oncogenic properties and all of which are overexpressed in multiple cancers 2.The kinetics of drug binding to gpcrs are complex and depend on several factors, including charge distribution on the receptor surface, ligand–receptor interactions in the binding channel and the binding site, or solvation. Previously, drugs were developed focusing on target affinity and selectivity. However, it is becoming evident that the drug–target residence time, related to the off-rate, is an important parameter for successful drug development. The residence time influences both the on-rate and overall effectiveness of drugs. Due to recent efforts in the development of fast computers, md simulations and related techniques allow calculation of the binding pathways of ligands and estimation of rate constants 3. Protease-activated receptors (pars) are a ubiquitously expressed class of g-protein-coupled receptors (gpcrs) that enable cells to respond to proteases in the extracellular environment in a nuanced and dynamic manner. Two agents targeting par1, recombinant activated protein c and vorapaxar, are US FDA approved. However, their use has been limited by questions of efficacy and safety, respectively.
 

  • Binding kinetics and pathways of ligands to GPCRs
  • Aurora A kinase ,a priority pharmaceutical target for treatment of cancer
  • Novel adjuvants designed for improving vaccine efficacy
  • Targetting Protease-activated receptors(PAR1)
  • Risks associated with new drug development

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