Bumped Kinase Inhibitor 1294 Treats Established Toxoplasma gondii Infection

被引：56

作者：

Doggett, J. Stone ^{[1
,2
]}

Ojo, Kayode K. ^{[3
]}

Fan, Erkang ^{[4
]}

Maly, Dustin J. ^{[5
]}

Van Voorhis, Wesley C. ^{[3
]}

机构：

[1] VA Med Ctr, Portland, OR 97239 USA

[2] Oregon Hlth & Sci Univ, Div Infect Dis, Portland, OR 97201 USA

[3] Univ Washington, Div Allergy & Infect Dis, Seattle, WA 98195 USA

[4] Univ Washington, Dept Biochem, Seattle, WA 98195 USA

[5] Univ Washington, Dept Chem, Seattle, WA 98195 USA

来源：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 2014年 / 58卷 / 06期

基金：

美国国家卫生研究院;

关键词：

1NM-PP1; POTENT; CDPK1;

D O I：

10.1128/AAC.01823-13

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Toxoplasma gondii is a unicellular parasite that causes severe brain and eye disease. Current drugs for T. gondii are limited by toxicity. Bumped kinase inhibitors (BKIs) selectively inhibit calcium-dependent protein kinases of the apicomplexan pathogens T. gondii, cryptosporidia, and plasmodia. A lead anti-Toxoplasma BKI, 1294, has been developed to be metabolically stable and orally bioavailable. Herein, we demonstrate the oral efficacy of 1294 against toxoplasmosis in vivo.

引用

页码：3547 / 3549

页数：3

共 12 条

[1] A Novel Calcium-Dependent Protein Kinase Inhibitor as a Lead Compound for Treating Cryptosporidiosis [J].

Castellanos-Gonzalez, Alejandro ;

White, A. Clinton, Jr. ;

Ojo, Kayode K. ;

Vidadala, Rama S. R. ;

Zhang, Zhongsheng ;

Reid, Molly C. ;

Fox, Anna M. W. ;

Keyloun, Katelyn R. ;

Rivas, Kasey ;

Irani, Ayesha ;

Dann, Sara M. ;

Fan, Erkang ;

Maly, Dustin J. ;

Van Voorhis, Wesley C. .

JOURNAL OF INFECTIOUS DISEASES, 2013, 208 (08) :1342-1348

[2] Acute toxoplasmoses in immunocompetent patients hospitalized in an intensive care unit in French Guiana [J].

Demar, M. ;

Hommel, D. ;

Djossou, F. ;

Peneau, C. ;

Boukhari, R. ;

Louvel, D. ;

Bourbigot, A. -M. ;

Nasser, V. ;

Ajzenberg, D. ;

Darde, M. -L. ;

Carme, B. .

CLINICAL MICROBIOLOGY AND INFECTION, 2012, 18 (07) :E221-E231

[3] Ocular Sequelae of Congenital Toxoplasmosis in Brazil Compared with Europe [J].

Gilbert, Ruth E. ;

Freeman, Katherine ;

Lago, Eleonor G. ;

Bahia-Oliveira, Lilian M. G. ;

Tan, Hooi Kuan ;

Wallon, Martine ;

Buffolano, Wilma ;

Stanford, Miles R. ;

Petersen, Eskild .

PLOS NEGLECTED TROPICAL DISEASES, 2008, 2 (08)

[4] Development of Toxoplasma gondii Calcium-Dependent Protein Kinase 1 (TgCDPK1) Inhibitors with Potent Anti-Toxoplasma Activity [J].

Johnson, Steven M. ;

Murphy, Ryan C. ;

Geiger, Jennifer A. ;

DeRocher, Amy E. ;

Zhang, Zhongsheng ;

Ojo, Kayode K. ;

Larson, Eric T. ;

Perera, B. Gayani K. ;

Dale, Edward J. ;

He, Panqing ;

Reid, Molly C. ;

Fox, Anna M. W. ;

Mueller, Natascha R. ;

Merritt, Ethan A. ;

Fan, Erkang ;

Parsons, Marilyn ;

Van Voorhis, Wesley C. ;

Maly, Dustin J. .

JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (05) :2416-2426

[5] Multiple Determinants for Selective Inhibition of Apicomplexan Calcium-Dependent Protein Kinase CDPK1 [J].

Larson, Eric T. ;

Ojo, Kayode K. ;

Murphy, Ryan C. ;

Johnson, Steven M. ;

Zhang, Zhongsheng ;

Kim, Jessica E. ;

Leibly, David J. ;

Fox, Anna M. W. ;

Reid, Molly C. ;

Dale, Edward J. ;

Perera, B. Gayani K. ;

Kim, Jae ;

Hewitt, Stephen N. ;

Hol, Wim G. J. ;

Verlinde, Christophe L. M. J. ;

Fan, Erkang ;

Van Voorhis, Wesley C. ;

Maly, Dustin J. ;

Merritt, Ethan A. .

JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (06) :2803-2810

[6] Optimizing Small Molecule Inhibitors of Calcium-Dependent Protein Kinase 1 to Prevent Infection by Toxoplasma gondii [J].

Lourido, Sebastian ;

Zhang, Chao ;

Lopez, Michael S. ;

Tang, Keliang ;

Barks, Jennifer ;

Wang, Qiuling ;

Wildman, Scott A. ;

Shokat, Kevan M. ;

Sibley, L. David .

JOURNAL OF MEDICINAL CHEMISTRY, 2013, 56 (07) :3068-3077

[7] Calcium-dependent protein kinase 1 is an essential regulator of exocytosis in Toxoplasma [J].

Lourido, Sebastian ;

Shuman, Joel ;

Zhang, Chao ;

Shokat, Kevan M. ;

Hui, Raymond ;

Sibley, L. David .

NATURE, 2010, 465 (7296) :359-U118

[8] Discovery of Potent and Selective Inhibitors of CDPK1 from C. parvum and T. gondii [J].

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. .

ACS MEDICINAL CHEMISTRY LETTERS, 2010, 1 (07) :331-335

[9] A Specific Inhibitor of PfCDPK4 Blocks Malaria Transmission: Chemical-genetic Validation [J].

Ojo, Kayode K. ;

Eastman, Richard T. ;

Vidadala, RamaSubbaRao ;

Zhang, Zhongsheng ;

Rivas, Kasey L. ;

Choi, Ryan ;

Lutz, Justin D. ;

Reid, Molly C. ;

Fox, Anna M. W. ;

Hulverson, Matthew A. ;

Kennedy, Mark ;

Isoherranen, Nina ;

Kim, Laura M. ;

Comess, Kenneth M. ;

Kempf, Dale J. ;

Verlinde, Christophe L. M. J. ;

Su, Xin-zhuan ;

Kappe, Stefan H. I. ;

Maly, Dustin J. ;

Fan, Erkang ;

Van Voorhis, Wesley C. .

JOURNAL OF INFECTIOUS DISEASES, 2014, 209 (02) :275-284

[10] Toxoplasma gondii calcium-dependent protein kinase 1 is a target for selective kinase inhibitors [J].

Ojo, Kayode K. ;

Larson, Eric T. ;

Keyloun, Katelyn R. ;

Castaneda, Lisa J. ;

DeRocher, Amy E. ;

Inampudi, Krishna K. ;

Kim, Jessica E. ;

Arakaki, Tracy L. ;

Murphy, Ryan C. ;

Zhang, Li ;

Napuli, Alberto J. ;

Maly, Dustin J. ;

Verlinde, Christophe L. M. J. ;

Buckner, Frederick S. ;

Parsons, Marilyn ;

Hol, Wim G. J. ;

Merritt, Ethan A. ;

Van Voorhis, Wesley C. .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2010, 17 (05) :602-U102

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