DEL-22379

Cas No.:	181223-80-3
Chemical Name:	N-[(3E)-3-[(5-Methoxy-1H-indol-3-yl)methylidene]-2-oxo-1H-indol-5-yl]-3-piperidin-1-ylpropanamide
Synonyms:	1-Piperidinepropanamide,N-[2,3-dihydro-3-[(5-methoxy-1H-indol-3-yl)methylene]-2-oxo-1H-indol-5-yl]-;DEL-22379;DEL22379;N-(3-((5-Methoxy-1H-indol-3-yl)methylene)-2-oxoindolin-5-yl)-3-(piperidin-1-yl)propanamide;N-[2,3-Dihydro-3-[(5-methoxy-1H-indol-3-yl)methylene]-2-oxo-1H-indol-5-yl]-1-piperidinepropanamide;DEL 22379;N-[(3E)-3-[(5-methoxy-1H-indol-3-yl)methylidene]-2-oxo-2,3-dihydro-1H-indol-5-yl]-3-(piperidin-1-yl)propanamide;N-[(3E)-3-[(5-Methoxy-1H-indol-3-yl)methylidene]-2-oxo-1H-indol-5-yl]-3-piperidin-1-ylpropanamide
SMILES:	O=C(C([H])([H])C([H])([H])N1C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H])N([H])C1C([H])=C([H])C2=C(C=1[H])/C(/C(N2[H])=O)=C(/[H])\C1=C([H])N([H])C2C([H])=C([H])C(=C([H])C1=2)OC([H])([H])[H]
Formula:	C26H28N4O3
M.Wt:	444.5255
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	DEL-22379 is an ERK dimerization Inhibitor. DEL-22379 readily binds to ERK2 with a Kd estimated in the low micromolar range, though binding is detectable even at low nanomolar concentrations. ERK2 dimerization is progressively inhibited with an IC50 of ~0.5 μM.
In Vivo:	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)[1].
In Vitro:	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[1].