Discovery and evaluation of novel inhibitors of mycobacterium protein tyrosine phosphatase B from the 6-Hydroxy-benzofuran-5-carboxylic acid scaffold.
Discovery and evaluation of novel inhibitors of mycobacterium protein tyrosine phosphatase B from the 6-Hydroxy-benzofuran-5-carboxylic acid scaffold.
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DOI：
10.1021/jm301781p
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发表时间：
2013-02-14
影响因子：
7.3
通讯作者：
Zhang, Zhong-Yin
中科院分区：
文献类型：
--
作者：
He, Yantao;Xu, Jie;Yu, Zhi-Hong;Gunawan, Andrea M.;Wu, Li;Wang, Lina;Zhang, Zhong-Yin
Mycobacterium tuberculosis (Mtb) protein tyrosine phosphatase B (mPTPB) is a virulence factor secreted by the pathogen and mediates mycobacterial survival in macrophages by targeting host cell immune responses. Consequently, mPTPB represents an exciting new target to combat TB infection. We describe a medicinal chemistry-oriented approach that transforms a benzofuran salicylic acid scaffold into a highly potent (IC50 = 38 nM) and selective mPTPB inhibitor (>50 fold against a large panel of PTPs). Importantly, the inhibitor is capable of reversing the altered host immune responses induced by the bacterial phosphatase and restoring the macrophage’s full capacity to secrete IL-6 and undergo apoptosis in response to IFN-γ stimulation, validating the concept that chemical inhibition of mPTPB may be therapeutically useful for novel TB treatment. The study further demonstrates that bicyclic salicylic acid pharmacophores can be used to deliver PTP inhibitors with high potency, selectivity, and cellular efficacy.
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影响因子：
15
作者：
Soellner, Matthew B.;Rawls, Katherine A.;Ellman, Jonathan A.
通讯作者：
Ellman, Jonathan A.
影响因子：
4.1
作者：
Correa, Ivan R., Jr.;Noeren-Mueller, Andrea;Waldmann, Herbert
通讯作者：
Waldmann, Herbert
凋亡是巨噬细胞对结核分枝杆菌的先天防御功能。
影响因子：
8
作者：
通讯作者：
--
DOI：
10.1007/s12094-006-0005-0
发表时间：
2006-03-01
期刊：
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
影响因子：
--
作者：
Ventura, Juan-Jose;Nebreda, Angel R
通讯作者：
Nebreda, Angel R
影响因子：
2.7
作者：
Weide, T;Arve, L;Kessler, H
通讯作者：
Kessler, H