Development of dual casein kinase 1δ/1ε (CK1δ/ε) inhibitors for treatment of breast cancer.

Abstract

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.

• Authors: Andrii Monastyrskyi, Napon Nilchan, Victor Quereda, Yoshihiko Noguchi, Claudia Ruiz, Wayne Grant, Michael Cameron, Derek Duckett, William Roush
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 26 Issue 3 Pg. 590-602 (02 01 2018) ISSN: 1464-3391 [Electronic] England
• PMID: 29289448 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

• Protein Kinase Inhibitors
• Casein Kinase 1 epsilon
• Casein Kinase Idelta

Topics

• Animals
• Binding Sites
• Casein Kinase 1 epsilon (antagonists & inhibitors, metabolism)
• Casein Kinase Idelta (antagonists & inhibitors, metabolism)
• Catalytic Domain
• Cell Line, Tumor
• Female
• Half-Life
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Microsomes, Liver (drug effects, metabolism)
• Molecular Docking Simulation
• Permeability (drug effects)
• Protein Kinase Inhibitors (chemistry, pharmacokinetics, pharmacology, therapeutic use)
• Rats
• Structure-Activity Relationship
• Transplantation, Heterologous
• Triple Negative Breast Neoplasms (drug therapy, metabolism, pathology)