Discovery of Potent and Selective Inhibitors of CDPK1 from C. parvum and T. gondii

作者：Murphy Ryan C; Ojo Kayode K; Larson Eric T; Castellanos Gonzalez Alejandro; Perera B Gayani K; Keyloun Katelyn R; Kim Jessica E; Bhandari Janhavi G; Muller Natascha R; Verlinde Christophe L M J; White A Clinton Jr; Merritt Ethan A; Van Voorhis Wesley C^*; Maly Dustin J

来源：ACS Medicinal Chemistry Letters, 2010, 1(7): 331-335.

DOI：10.1021/ml1000961

• Phosphorylation
• protozoans
• calcium-dependent protein kinases
• Cryptosporidium parvum
• Toxoplasma gondii
• apicomplexan

The protozoans Cryptosporidium parvum and Toxoplasma gondii are parasites of major health concern to humans. Both parasites contain a group of calcium dependent protein kinases (CDPKs) which are found in plants and ciliates but not in humans or fungi. Here, we describe a series of potent inhibitors that target CDPK1 in C. parvum (CpCDPK1) and T. gondii (TgCDPK1). These inhibitors are highly selective for CpCDPK1 and TgCDPK1 over the mammalian kinases SRC and ABL. Furthermore, they are able to block an early stage of C. parvum invasion of HCT-8 host cells, which is similar to their effects on T. gondii invasion of human fibroblasts.

• 出版日期2010-10