Bumped Kinase Inhibitor 1294 Treats Established Toxoplasma gondii Infection

被引：55
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
收藏
页码：3547 / 3549
页数：3
相关论文
共 12 条
  • [1] A Novel Calcium-Dependent Protein Kinase Inhibitor as a Lead Compound for Treating Cryptosporidiosis
    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.
    [J]. JOURNAL OF INFECTIOUS DISEASES, 2013, 208 (08) : 1342 - 1348
  • [2] Acute toxoplasmoses in immunocompetent patients hospitalized in an intensive care unit in French Guiana
    Demar, M.
    Hommel, D.
    Djossou, F.
    Peneau, C.
    Boukhari, R.
    Louvel, D.
    Bourbigot, A. -M.
    Nasser, V.
    Ajzenberg, D.
    Darde, M. -L.
    Carme, B.
    [J]. CLINICAL MICROBIOLOGY AND INFECTION, 2012, 18 (07) : E221 - E231
  • [3] Ocular Sequelae of Congenital Toxoplasmosis in Brazil Compared with Europe
    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
    [J]. PLOS NEGLECTED TROPICAL DISEASES, 2008, 2 (08):
  • [4] Development of Toxoplasma gondii Calcium-Dependent Protein Kinase 1 (TgCDPK1) Inhibitors with Potent Anti-Toxoplasma Activity
    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.
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (05) : 2416 - 2426
  • [5] Multiple Determinants for Selective Inhibition of Apicomplexan Calcium-Dependent Protein Kinase CDPK1
    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.
    [J]. 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
    Lourido, Sebastian
    Zhang, Chao
    Lopez, Michael S.
    Tang, Keliang
    Barks, Jennifer
    Wang, Qiuling
    Wildman, Scott A.
    Shokat, Kevan M.
    Sibley, L. David
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2013, 56 (07) : 3068 - 3077
  • [7] Calcium-dependent protein kinase 1 is an essential regulator of exocytosis in Toxoplasma
    Lourido, Sebastian
    Shuman, Joel
    Zhang, Chao
    Shokat, Kevan M.
    Hui, Raymond
    Sibley, L. David
    [J]. NATURE, 2010, 465 (7296) : 359 - U118
  • [8] Discovery of Potent and Selective Inhibitors of CDPK1 from C. parvum and T. gondii
    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.
    [J]. ACS MEDICINAL CHEMISTRY LETTERS, 2010, 1 (07): : 331 - 335
  • [9] A Specific Inhibitor of PfCDPK4 Blocks Malaria Transmission: Chemical-genetic Validation
    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.
    [J]. JOURNAL OF INFECTIOUS DISEASES, 2014, 209 (02) : 275 - 284
  • [10] Toxoplasma gondii calcium-dependent protein kinase 1 is a target for selective kinase inhibitors
    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.
    [J]. NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2010, 17 (05) : 602 - U102
12