Structure-guided development of selective TbcatB inhibitors

Jeremy P. Mallari; Anang A. Shelat; Aaron Kosinski; Conor R. Caffrey; Michele Connelly; Fangyi Zhu; James H. McKerrow; R. Kiplin Guy

doi:10.1021/jm900908p

Structure-guided development of selective TbcatB inhibitors

Jeremy P. Mallari, Anang A. Shelat, Aaron Kosinski, Conor R. Caffrey, Michele Connelly, Fangyi Zhu, James H. McKerrow, R. Kiplin Guy

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

Abstract

The trypanosomal cathepsin TbcatB is essential for parasite survival and is an attractive therapeutic target. Herein we report the structure-guided development of TbcatB inhibitors with specificity relative to rhodesain and human cathepsins B and L. Inhibitors were tested for enzymatic activity, trypanocidal activity, and general cytotoxicity. These data chemically validate TbcatB as a drug target and demonstrate that it is possible to potently and selectively inhibit TbcatB relative to trypanosomal and human homologues.

Original language	English
Pages (from-to)	6489-6493
Number of pages	5
Journal	Journal of Medicinal Chemistry
Volume	52
Issue number	20
DOIs	https://doi.org/10.1021/jm900908p
State	Published - Oct 22 2009

Funding

Funders	Funder number
National Institute of Allergy and Infectious Diseases	P01AI035707

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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10.1021/jm900908p

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title = "Structure-guided development of selective TbcatB inhibitors",

abstract = "The trypanosomal cathepsin TbcatB is essential for parasite survival and is an attractive therapeutic target. Herein we report the structure-guided development of TbcatB inhibitors with specificity relative to rhodesain and human cathepsins B and L. Inhibitors were tested for enzymatic activity, trypanocidal activity, and general cytotoxicity. These data chemically validate TbcatB as a drug target and demonstrate that it is possible to potently and selectively inhibit TbcatB relative to trypanosomal and human homologues.",

author = "Mallari, {Jeremy P.} and Shelat, {Anang A.} and Aaron Kosinski and Caffrey, {Conor R.} and Michele Connelly and Fangyi Zhu and McKerrow, {James H.} and {Kiplin Guy}, R.",

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doi = "10.1021/jm900908p",

language = "English",

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T1 - Structure-guided development of selective TbcatB inhibitors

AU - Mallari, Jeremy P.

AU - Shelat, Anang A.

AU - Kosinski, Aaron

AU - Caffrey, Conor R.

AU - Connelly, Michele

AU - Zhu, Fangyi

AU - McKerrow, James H.

AU - Kiplin Guy, R.

PY - 2009/10/22

Y1 - 2009/10/22

N2 - The trypanosomal cathepsin TbcatB is essential for parasite survival and is an attractive therapeutic target. Herein we report the structure-guided development of TbcatB inhibitors with specificity relative to rhodesain and human cathepsins B and L. Inhibitors were tested for enzymatic activity, trypanocidal activity, and general cytotoxicity. These data chemically validate TbcatB as a drug target and demonstrate that it is possible to potently and selectively inhibit TbcatB relative to trypanosomal and human homologues.

AB - The trypanosomal cathepsin TbcatB is essential for parasite survival and is an attractive therapeutic target. Herein we report the structure-guided development of TbcatB inhibitors with specificity relative to rhodesain and human cathepsins B and L. Inhibitors were tested for enzymatic activity, trypanocidal activity, and general cytotoxicity. These data chemically validate TbcatB as a drug target and demonstrate that it is possible to potently and selectively inhibit TbcatB relative to trypanosomal and human homologues.

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EP - 6493

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 20

ER -

Structure-guided development of selective TbcatB inhibitors

Abstract

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ASJC Scopus subject areas

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