The extracellular regulated protein kinases (ERK) play important roles in regulating cellular proliferation and survival. DEL-22379 is a small molecule inhibitor of ERK dimerization with an IC50 value of ~0.5μM. It inhibited ERK dimerization in DLD1 (KRAS mutant), RKO (BRAF mutant) and T47D (WT/WT) cell lines at concentrations of 0.1-10μM. Treatment with DEL-22379 (10μM) for 12 h induced apoptosis in tumor cell lines harboring oncogenic RAS or BRAF. In mouse xenograft models, the treatment with DEL-22379 (15mg/kg/day) for 15 days significantly inhibited the progression of tumors derived from A375 cells (BRAF mutant) but not in mice injected with CHL cells (WT/WT). In a mouse model of BRAF mutant colorectal cancer patient-derived xenograft, the treatment with DEL-22379 (15mg/kg/day) for 21 days markedly suppressed tumor growth compared to the control group[2].
作用机制
DEL-22379 inhibits ERK dimerization by binding to ERK2 within the dimerization interface[2].
DEL-22379 细胞实验
Cell Line
Concentration
Treated Time
Description
References
OCUT2
1-10 µM
30 minutes
DEL-22379 impaired ERK dimerization and reduced ERK and RSK phosphorylation in BRAF-mutant cells.
Cell Mol Life Sci. 2022 Sep 3;79(9):504.
HTH83
1-10 µM
30 minutes
DEL-22379 failed to impair ERK dimerization in RAS-mutant cells.
Cell Mol Life Sci. 2022 Sep 3;79(9):504.
CAL62
1-10 µM
30 minutes
DEL-22379 failed to impair ERK dimerization in RAS-mutant cells.
Cell Mol Life Sci. 2022 Sep 3;79(9):504.
DEL-22379 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Nude mice
Orthotopic ATC model
Intraperitoneal injection
15 mg/kg
Every 12 hours
DEL-22379 significantly inhibited tumor growth and metastatic dissemination in BRAF-mutant cells, with some effect on RAS-mutant cells.
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