Product Name: CCT-251545

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CAT#: A-1387


  Synonym:CCT-251545,

CCT-251545 Chemical Structure
CCT-251545 chemical structure


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IUPAC/Chemical name:

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Biological Activity
a potent and selective small molecule WNT pathway inhibitor
Technical Data
Purity: >99%
Storage Conditions: 2ºC to 8 ºC, or -20ºC for 3 years.

Reference
http://www.ncbi.nlm.nih.gov/pubmed/25680029
WNT signaling is frequently deregulated in malignancy, particularly in colon cancer, and plays a key role in the generation and maintenance of cancer stem cells. We report the discovery and optimization of a 3,4,5-trisubstituted pyridine 9 using a high-throughput cell-based reporter assay of WNT pathway activity. We demonstrate a twisted conformation about the pyridine-piperidine bond of 9 by small-molecule X-ray crystallography. Medicinal chemistry optimization to maintain this twisted conformation, cognisant of physicochemical properties likely to maintain good cell permeability, led to 74 (CCT251545), a potent small-molecule inhibitor of WNT signaling with good oral pharmacokinetics. We demonstrate inhibition of WNT pathway activity in a solid human tumor xenograft model with evidence for tumor growth inhibition following oral dosing. This work provides a successful example of hypothesis-driven medicinal chemistry optimization from a singleton hit against a cell-based pathway assay without knowledge of the biochemical target.