دانلود مقاله با موضوع بینش در مورد ویژگی ها و بهینه سازی سرب بازدارنده های جدید نوع 1
در قالب pdf و در 12 اسلاید،قابل ویرایش، شامل:
موضوع به انگلیسی:Insights into features and lead optimization of novel type 1½inhibitors of
p38α mitogen-activated protein kinase using QSAR, quantum
mechanics, bioisostere replacement and ADMET studies
بخشی از متن:p38α mitogen-activated protein kinase (p38αMAPK) has been implicated in many diseases yet no inhibitor has
been approved for therapeutic use. Various inhibitors have been developed with different binding modes, but
none has been approved for use due to the non-specificity of these inhibitors. A novel type of inhibitor developed
by Walter et al., and termed Type 1½, showed promising results in vitro with high selectivity for p38αMAPK, improved
target retention time (TRT) and high potency. Type 1½ inhibitors combine features of both Type I inhibitors
and Type II inhibitors. In this study, we provide insight into these novel inhibitors using QSAR, Molecular
docking, and Quantum mechanics. Finally, in a bid to optimize, we generated 523 new sets of lead compounds
using Bioisostere replacement methods and predicted the biological activities using the well-validated QSAR
model. The results showed that the nhal descriptor (Count of halogen atoms) was the most important contributor
to the QSAR model and the newly designed leads showed improved binding free energy than the original inhibitors
with predicted pIC50 up to 3.2
