Development of dual casein kinase 1δ/1ε (CK1δ/ε) inhibitors for treatment of breast cancer. Issue 3 (1st February 2018)

• Record Type: Journal Article
• Authors: Monastyrskyi, Andrii; Nilchan, Napon; Quereda, Victor; Noguchi, Yoshihiko; Ruiz, Claudia; Grant, Wayne; Cameron, Michael; Duckett, Derek; Roush, William
• Is Part Of: Bioorganic & medicinal chemistry. Volume 26:Issue 3(2018)
• Page Start: 590
• Page End: 602
• Publication Date: 2018-02-01
• Subjects: Casein kinase 1 delta and epsilon -- Kinase -- Inhibitor -- Structure-activity relationship -- Breast cancer; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2017.12.020
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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.