UNASSIGNED: It has been previously shown that the inhibition of @entity8047 ( @entity8047 ) contributes to apoptosis and suppression of different @entity5 cells. Correspondingly, a number of @entity16629 inhibitors have been designed and evaluated since 2001. However, they did not satisfy essential pharmacokinetic (PK) and pharmacodynamic (PD) properties thus, almost most of them were terminated in pre-clinical or clinical studies. This study aims to design new specific @entity16629 inhibitors with improved PK/PD profiles to be used as alternative @entity5 medications. In first part of this study, a comprehensive screening, for the first time, was done on well-known @entity16629 inhibitors using a number of computational programs such as AutoDock Tools 4.2 (ADT) and AutoDock Vina. Therefore a valuable training dataset as well as a reliable pharmacophore model were provided which were then used to design new inhibitors. According to the results of training dataset, @entity5459 was determined as the best inhibitor provided, so far. So, @entity5459 was used as the lead structure to design new inhibitors in this study. In second part of this investigation, a set of new allosteric @entity16629 inhibitors were designed significantly improving the binding energy as well as the ADMET properties, suggesting more specific and stable ligand-receptor complexes. Consequently, the structures 14 and 15 of our inhibitors, as the most potent structures, are great substituents for @entity5459 to be used and evaluated in clinical trials as alternative @entity5 drugs.

In silico investigation of new binding pocket for mitogen activated kinase kinase ( XXXX ): Development of new promising inhibitors.

@entity5 :: ('MESH:D009369', 'Disease') :: ['cancer'] @entity5459 :: ('MESH:C560077', 'Chemical') :: ['Trametinib'] @entity8047 :: ('5609', 'Gene') :: ['mitogen activated protein kinase kinase', 'MEK'] @entity16629 :: ('5604;5605', 'Gene') :: ['MEK1/2']
@entity8047 :: (5609,Gene) :: ['MEK']
