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Discovery and structure activity relationship of the first potent cryptosporidium FIKK kinase inhibitor.

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 identified 4b as a potent (IC50=0.2nM) 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.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Osman KT,Ye J,Shi Z,Toker C,Lovato D,Jumani RS,Zuercher W,Huston CD,Edwards AM,Lautens M,Santhakumar V,Hui R

doi

10.1016/j.bmc.2017.01.036

subject

Has Abstract

pub_date

2017-03-01 00:00:00

pages

1672-1680

issue

5

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(16)31438-9

journal_volume

25

pub_type

杂志文章

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