product name DEL-22379
Description: DEL-22379 is a potent, selective, and water-soluble ERK dimerization inhibitor with IC50 of 0.5 μM. DEL-22379 inhibits ERK Dimerization without affecting ERK phosphorylation, forestalls tumorigenesis driven by RAS-ERK pathway oncogenes. Nearly 50% of human malignancies exhibit unregulated RAS-ERK signaling; inhibiting it is a valid strategy for antineoplastic intervention.
References: Cancer Cell. 2015 Aug 10;28(2):170-82.
444.53
Formula
C26H28N4O3
CAS No.
181223-80-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 89 mg/mL (200.2 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19415578
| In Vitro |
In vitro activity: DEL-22379 inhibits ERK dimerization without affecting its phosphorylation. In a panel of human cell lines harboring mutant BRAF (V600E) or RAS (Q61L or G12V), DEL-22379 shows potent anti-proliferative effects, and induces apoptosis. Kinase 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). Cell Assay: Cellular proliferation is analyzed by Alamar blue assays. Briefly, Cells (A panel of human cell lines harboring mutant BRAF (V600E) or RAS (Q61L or G12V)) 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. |
|---|---|
| In Vivo | DEL-22379 (15 mg/kg, i.p.) prevents tumor growth and metastasis in mice bearing A375 (BRAF mutant) and HCT116 (KRAS mutant) tumors, but fails to prevent the formation of tumors in mice injected with CHL cells (WT/WT). |
| Animal model | Nude mice bearing A375 (BRAF mutant), CHL (WT/WT) or HCT116 (KRAS mutant) tumors |
| Formulation & Dosage | Dissolved in 1% DMSO; 15 mg/kg; i.p. |
| References | Cancer Cell. 2015 Aug 10;28(2):170-82. |
