ETC-159 is a potent, selective and orally available PORCN inhibitor, which inhibits β-catenin reporter activity with an IC50 of 2.9 nM. ETC-159 blocks the secretion and activity of all Wnts. ETC-159 has robust activity in multiple cancer models driven by high Wnt signaling.
ETC-159 is remarkably effective in treating RSPO-translocation bearing colorectal cancer (CRC) patient-derived xenografts. ETC-159 inhibits mouse PORCN with an IC50 of 18.1 nM, whereas the IC50 for Xenopus Porcn is approximately four fold higher (70 nM). ETC-159 exhibits good oral pharmacokinetics in mice allowing preclinical evaluation via oral administration. After a single oral dose of 5 mg/kg, ETC-159 is rapidly absorbed into the blood with a Tmax of ~0.5 h and oral bioavailability of 100%
|Cell lines||HEK293 cells, STF3A cells|
|Preparation method||HEK293 cells stably transfected with STF reporter and pPGK-WNT3A plasmid (STF3A cells) are treated with varying concentrations of compounds. For Wnt secretion, STF3A cells are treated with ETC-159 diluted in 1% fetal bovine serum-containing media.|
|Incubation time||24 h|
|Formulation||Formulated in 50% PEG400 (vol/vol) in water|
|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 Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 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 Compound A of 10 mg/kg.
|Solubility||DMSO: ≥ 25 mg/mL|
|Related Wnt/beta-catenin Products|
NLS-StAx-h is a selective fixed peptide inhibitor of Wnt signaling,IC50 1.4 μM.
Methyl vanillate, an extract found in the genus Loquat, is a Wnt/β-catenin signaling pathway activator. Benzoate, is the methyl ester of vanillin. It has antioxidant effects. Plant metabolites.
L-Quebrachitol is a natural product isolated from a variety of plants that promotes osteoblast production by upregulating BMP-2, runt-associated transcription factor (Runx2), MAPK (ERK, JNK, p38α), and Wnt/β-catenin signaling pathways.
PRI-724 (C-82 prodrug, ICG-001 analog) is a potent, specific inhibitor that disrupts the interaction of β-catenin and CBP
Foxy-5 TFA, a WNT5A agonist, is a mimicking peptide of WNT5A which is a non-canonical member of the Wnt family. Foxy-5 TFA triggers cytosolic free calcium signaling without affecting β-catenin activation and it impairs the migration and invasion of epithelial cancer cells.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2020 AbMole BioScience. All Rights Reserved.