su-11248 and Triple-Negative-Breast-Neoplasms

Casein kinase 1δ/ε have been identified as promising therapeutic target for oncology application, including breast and brain cancer. Here, we described our continued efforts in optimization of a lead series of purine scaffold inhibitors that led to identification of two new CK1δ/ε inhibitors 17 and 28 displaying low nanomolar values in antiproliferative assays against the human MDA-MB-231 triple negative breast cancer cell line and have physical, in vitro and in vivo pharmacokinetic properties suitable for use in proof of principle animal xenograft studies against human cancers.

Topics: Animals; Binding Sites; Casein Kinase 1 epsilon; Casein Kinase Idelta; Catalytic Domain; Cell Line, Tumor; Female; Half-Life; Humans; Male; Mice; Mice, Inbred C57BL; Microsomes, Liver; Molecular Docking Simulation; Permeability; Protein Kinase Inhibitors; Rats; Structure-Activity Relationship; Transplantation, Heterologous; Triple Negative Breast Neoplasms