PD318088 is a non-ATP competitive allosteric MEK1/2 inhibitor, binding simultaneously with ATP in a region of the MEK1 active site that is adjacent to the ATP-binding site.

PD318088是一种小分子抑制剂，针对MEK1/2，可作为PD184352的类似物，暗示其可能对癌细胞具有显著的抗增殖活性。PD318088与ATP同时结合于MEK1活性位点的相邻区域，该区域毗邻ATP结合位点。与PD318088和MgATP形成的三元复合体导致MEK1和MEK2的Kd单体-二聚体适度增加（至140nM）。PD318088和MgATP的结合也阻止了MEK1的四聚体和更高级别聚集体的形成。PD318088和MgATP共同作用轻微增加了MEK1和MEK2的二聚体解离常数，由约75nM增至约140nM，表明PD318088的抑制机制可能是由于活性位点的局部构象变化，而非整体结构的全局变化。[1]

Enzyme Assays: Phosphatidylinositide 3-kinase inhibitory activity was determined using a scintillation proximity assay in the presence of 1 μmol/L ATP. Inhibition of mTOR protein kinase was determined using a TR-FRET-based LanthaScreen method from Invitrogen. Compounds were assayed at a maximum concentration of 10 μmol/L in the presence of 1 μmol/L ATP, and IC50 values were determined using GraphPad Prism software.