DEL-22379 is a water-soluble ERK dimerization inhibitor with IC50 of ～0.5 μM.

ERK:0.5 μM

DEL-22379抑制了ERK二聚体的形成，但不影响其磷酸化。在携带突变BRAF (V600E)或RAS (Q61L或G12V)的人类细胞系中，DEL-22379显示出强大的抗增殖效果，并诱导凋亡。[1]

DEL-22379（15 mg/kg，i.p.）在携带A375（BRAF突变）和HCT116（KRAS突变）肿瘤的小鼠中阻止了肿瘤生长和转移，但未能阻止注射CHL细胞（WT/WT）的小鼠中肿瘤的形成。[1]

ERK dimerization assay: Compound screening is performed in HEK293T cells treated with the potential inhibitors (10 μM) for 30 min before EGF stimulation. Cellular lysates are tested for ERK dimerization by native PAGE and p-ERK evaluation of the potential positives. In vitro ERK dimerization is assayed using GST-MEK1 ΔN EE purified from bacteria, bound to glutathione sepharose beads, and incubated with 25 μg/ml of purified His-ERK2 plus increasing concentrations of DEL-22379. Western blotting, kinase assays, and luciferase assays are also performed. In silico docking of the DEL-22379 compound is carried out with the modeling tools provided by the OpenEye package (v. 2.1).

Cellular proliferation is analyzed by Alamar blue assays. Briefly, Cells are plated in 96-well plates at a density of 1000-2000 cells per well. Cells are treated with drug concentrations prepared by serial dilution ranging from 0.1 nM to 10 μM. 48 hr after drug treatment cells are exposed to Alamar Blue and the colorimetric change is measured at 570 and 600 nm. GI50 is estimated by nonlinear regression using GraphPad5 Prism Software.(Only for Reference)