Discovery and structure activity relationship of the first potent cryptosporidium FIKK kinase inhibitor. Issue 5 (1st March 2017)

• Record Type: Journal Article
• Authors: Osman, Khan T.; Ye, Juntao; Shi, Zhihao; Toker, Christina; Lovato, Diogo; Jumani, Rajiv S.; Zuercher, William; Huston, Christopher D.; Edwards, Aled M.; Lautens, Mark; Santhakumar, Vijayaratnam; Hui, Raymond
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 5(2017)
• Page Start: 1672
• Page End: 1680
• Publication Date: 2017-03-01
• Subjects: Cryptosporidium -- Kinase inhibitor -- FIKK Kinase inhibitor; 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.2017.01.036
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: FIKKs are parasite-specific protein kinases with distinctive sequence motifs and their biological roles have not been completely elucidated. Here, we report the first potent Cryptosporidium FIKK (CpFIKK) inhibitor. We identified4b as a potent (IC50 = 0.2 nM) inhibitor of CpFIKK catalytic activity. In addition, we identified both CpCDPK1 selective as well as dually acting CpFIKK-CDPK1 inhibitors from the same structural class of compounds. We evaluated these CpFIKK inhibitors for inhibition of parasite growth in vitro . The observed effects on parasite growth did not correlate with CpFIKK inhibition, suggesting that CpFIKK may not be involved in parasite growth.