In vitro: 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. 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).
|Cell lines||A panel of human cell lines harboring mutant BRAF (V600E) or RAS (Q61L or G12V)|
|Preparation method||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.|
|Incubation time||48 h|
|Animal models||Nude mice bearing A375 (BRAF mutant), CHL (WT/WT) or HCT116 (KRAS mutant) tumors|
|Dosages||15 mg/kg, bid|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||89 mg/mL in DMSO|
Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes.
Herrero A, et al. Cancer Cell. 2015 Aug 10;28(2):170-82. PMID: 26267534.
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