ETC-159

Cas：1638250-96-0

Product Information：

ETC-159, also known as ETC-1922159, is a potent, selective and orally available PORCN inhibitor. ETC-159 blocks the secretion and activity of all Wnts. ETC-159 is remarkably effective in treating RSPO-translocation bearing colorectal cancer (CRC) patient-derived xenografts. Inhibition of Wnt signaling by PORCN inhibition holds promise as differentiation therapy in genetically defined human cancers. Enhanced sensitivity to Wnts is an emerging hallmark of a subset of cancers, defined in part by mutations regulating the abundance of their receptors.

Chemical Formula: C19H19N7O3

Exact Mass: 393.15494

Molecular Weight: 393.407

Elemental Analysis: C, 58.01; H, 4.87; N, 24.92; O, 12.20

Chemical Name: 

1,3-dimethyl-7-((6-phenylpyridazin-3-yl)glycyl)-3,4,5,7-tetrahydro-1H-purine-2,6-dione

InChi Key:

COEZTQWWLJCBEC-UHFFFAOYSA-N

InChi Code: 

InChI=1S/C19H19N7O3/c1-24-17-16(18(28)25(2)19(24)29)26(11-21-17)15(27)10-20-14-9-8-13(22-23-14)12-6-4-3-5-7-12/h3-9,11,16-17H,10H2,1-2H3,(H,20,23)

Smiles Code:

O=C1C2C(N=CN2C(CNC3=CC=C(C4=CC=CC=C4)N=N3)=O)N(C)C(N1C)=O

Technical Data：

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

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.

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%.

References:

1. Madan B, Ke Z, Harmston N, Ho SY, Frois AO, Alam J, Jeyaraj DA, Pendharkar V, Ghosh K, Virshup IH, Manoharan V, Ong EH, Sangthongpitag K, Hill J, Petretto E, Keller TH, Lee MA, Matter A, Virshup DM. Wnt addiction of genetically defined cancers reversed by PORCN inhibition. Oncogene. 2015 Aug 10. doi: 10.1038/onc.2015.280. [Epub ahead of print] PubMed PMID: 26257057.

Products are for research use only. Not for human use.