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

Access to Document

10.1021/jm900908p

Cite this

@article{99eef0e5f0664716a4b6a481b5679a25,

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.",

year = "2009",

month = oct,

day = "22",

doi = "10.1021/jm900908p",

language = "English",

volume = "52",

pages = "6489--6493",

number = "20",

}

TY - JOUR

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.

UR - https://www.scopus.com/pages/publications/70350057084

UR - https://www.scopus.com/pages/publications/70350057084#tab=citedBy

U2 - 10.1021/jm900908p

DO - 10.1021/jm900908p

M3 - Article

C2 - 19769357

AN - SCOPUS:70350057084

SN - 0022-2623

VL - 52

SP - 6489

EP - 6493

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 20

ER -

Structure-guided development of selective TbcatB inhibitors

Abstract

Funding

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this