DEL-22379

Research use only, not for human use.

A small molecule inhibitor of ERK dimerization with IC50 of 0.5 uM, without affecting ERK phosphorylation.

A small molecule inhibitor of ERK dimerization with IC50 of 0.5 uM, without affecting ERK phosphorylation; prevents tumorigenesis by RAS-ERK pathway oncogenes.

DEL-22379 is an ERK dimerization inhibitor. DEL-22379 abolishes EGF-induced co-immunoprecipitation of ectopic ERK2 molecules tagged with hemagglutinin (HA) or FLAG epitopes, with an estimated half-maximal inhibitory concentration (IC50) of ~0.5 μM. DEL-22379 inhibits growth of tumor cells harboring RAS-ERK pathway oncogenes. The biological effects of DEL-22379 are investigated on tumor cells in culture. The cytostatic effects of DEL-22379 are compared to those of the MEK inhibitor PD-0325901 and the ERK kinase inhibitor SCH-772984, as reflected by their half-maximal growth inhibitory concentrations (GI50). Cell lines harboring mutant BRAF are the most sensitive to the three compounds. In comparison, wild-type (WT) cell lines for BRAF and RAS are the most resistant, and RAS mutant cells exhibit a range of sensitivities. In cells showing different oncogenic genotypes, distinct sensitivity to DEL-22379 can not be attributed to variations on its effects on dimerization, because DEL-22379 displays similar dimerization- and cytoplasmic signaling-inhibitory dose responses (IC50 of 150-400 nM) regardless of the genotype.

To test DEL-22379 antitumor effects, some of the aforementioned cell lines are xenografted into nude mice, and tumor growth is monitored after intra-peritoneal administration of DEL-22379 at 15 mg/kg. At such a dose, inhibition of ERK dimerization is evident in liver extracts and in xenografted tumors. DEL-22379 markedly inhibits tumor progression for A375 cells (BRAF mutant).

DEL22379 | DEL 22379

MAPK/ERK Signaling

ERK

ERK

Cancer

——

181223-80-3

444.5255

C26H28N4O3

>98% (HPLC)

DMSO: ≥ 30 mg/mL

O=C(NC1=CC2=C(NC(/C2=C/C3=CNC4=C3C=C(OC)C=C4)=O)C=C1)CCN5CCCCC5

1-Piperidinepropanamide, N-[2,3-dihydro-3-[(5-methoxy-1H-indol-3-yl)methylene]-2-oxo-1H-indol-5-yl]-

(-20℃)

With Ice Pack

≥ 2 years