PD318088 是非 ATP 竞争性的MEK1/2变构抑制剂，是 PD184352 的结构类似物。它在MEK1 活性位点与 ATP 结合位点相邻的区域与 ATP 同时结合，可用于癌症研究。

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 is a small-molecule inhibitor of MEK1/2, which is an analog of PD184352, suggesting it might have substantial anti-proliferative activity against cancer cells, although no functional study of PD318088 is currently available. PD318088 binds simultaneously with ATP in a region of the MEK1 active site that is adjacent to the ATP-binding site. Formation of the ternary complexes with PD318088 and MgATP results in moderate increases (to 140 nM) for the Kd monomer-dimer for both MEK1 and MEK2. The binding of PD318088 and MgATP to MEK1 also abolishes the formation of tetramers and higher-order aggregates. PD318088 and MgATP together increase the dimerization disassociation constant for MEK1 and MEK2 slightly from ~75 nM to ~140 nM, suggesting that the mechanism of inhibition for PD318088 is probably a result of localized conformational changes in the active site and not a global change in the overall structure. [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.

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C16H13BrF3IN2O4

561.094

DMSO:112 mg/mL (199.61 mM)
H2O:<1 mgml
Ethanol:14 mg/mL (24.95 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years