ETC-159
Names
[ CAS No. ]:
1638250-96-0
[ Name ]:
ETC-159
[Synonym ]:
2-(1,3-Dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(6-phenyl-3-pyridazinyl)acetamide
7H-Purine-7-acetamide, 1,2,3,6-tetrahydro-1,3-dimethyl-2,6-dioxo-N-(6-phenyl-3-pyridazinyl)-
ETC-159
Biological Activity
[Description]:
ETC-159 is a potent, orally available PORCN inhibitor. It inhibits β-catenin reporter activity with an IC50 of 2.9 nM.
[Related Catalog]:
[Target]
IC50: 2.9 nM (β-catenin)[1]
[In Vitro]
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 highly efficacious in molecularly defined colorectal cancers (CRCs) with R-spondin translocations[1]
[In Vivo]
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 is remarkably effective in treating RSPO-translocation bearing colorectal cancer (CRC) patient-derived xenografts. 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%[1].
[Cell Assay]
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[1].
[Animal admin]
Mice: For human xenograft models, patient-derived solid tissue fragments are subcutaneously implanted in BALB/c nude mice. All groups are matched for tumor size with equal variance before treatment. ETC-159 formulated in 50% PEG400 (vol/vol) in water is administered by oral gavage at a dosing volume of 10 μL/g body weight[1].
[References]
[Related Small Molecules]
Chemical & Physical Properties
[ Density]:
1.5±0.1 g/cm3
[ Molecular Formula ]:
C19H17N7O3
[ Molecular Weight ]:
391.383
[ Exact Mass ]:
391.139282
[ LogP ]:
1.20
[ Index of Refraction ]:
1.732
[ Storage condition ]:
2-8℃