Selective inhibition of Sarcocystis neurona calcium-dependent protein kinase 1 for equine protozoal myeloencephalitis therapy

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• 作者：Kayode K. Ojo^a ; ^{ojo67kk@u.washington.edu} ; Sriveny Dangoudoubiyam^b ; Shiv K. Verma^c ; Suzanne Scheele^d ; Amy E. DeRocher^d ; Michelle Yeargan^e ; Ryan Choi^a ; Tess R. Smith^a ; Kasey L. Rivas^a ; Matthew A. Hulverson^a ; Lynn K. Barrett^a ; Erkang Fan^f ; Dustin J. Maly^g ; Marilyn Parsons^d ; ^h ; Jitender P. Dubey^c ; Daniel K. Howe^e ; ^{daniel.howe@uky.edu} ; Wesley C. Van Voorhis^a ; ^h ; ^{wesley@uw.edu}
• 关键词：Sarcocystis neurona ; Equine protozoal myeloencephalitis ; Calcium-dependent protein kinase 1 ; Gatekeeper residue ; Drug target ; Bumped kinase inhibitors
• 刊名：International Journal for Parasitology
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：46
• 期：13-14
• 页码：871-880
• 全文大小：1503 K
• 卷排序：46

文摘

Sarcocystis neurona (Sn) CDPK1 has an atypical small gatekeeper residue selectively inhibited by BKIs. Evidence is provided that shows SnCDPK1 is a potential target for rational EPM drug development. Bumped kinase inhibitors interfered with an early step in S. neurona tachyzoite host cell invasion. Nine of 10 mice in a BKI-1553 experimentally treated group were cured of equine protozoal myeloencephalitis.