In:
ChemMedChem, Wiley, Vol. 5, No. 12 ( 2010-12-03), p. 2051-2056
Abstract:
Tuberculosis (TB), which is caused by Mycobacterium tuberculosis (Mtb), is a major worldwide threat to public health. Mycobacterium protein tyrosine phosphatase B (mPTPB) is a virulent phosphatase secreted by Mtb, which is essential for the survival and persistence of the bacterium in the host. Consequently, small‐molecule inhibitors of mPTPB are expected to serve as anti‐TB agents with a novel mode of action. Herein, we report the discovery of highly potent and selective mPTPB inhibitors using a novel, double Click chemistry strategy. The most potent mPTPB inhibitor from this approach possesses a K i value of 160 n M and a 〉 25‐fold selectivity for mPTPB over 19 other protein tyrosine phosphatases (PTBs). Molecular docking study of the enzyme–inhibitor complex provides a rationale for the high potency and selectivity of the lead compound and reveals an unusual binding mode, which may guide further optimization effort.
Type of Medium:
Online Resource
ISSN:
1860-7179
,
1860-7187
DOI:
10.1002/cmdc.201000348
Language:
English
Publisher:
Wiley
Publication Date:
2010
detail.hit.zdb_id:
2209649-8
SSG:
15,3
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