Inhibition of lymphoid tyrosine phosphatase by benzofuran salicylic acids.
Inhibition of lymphoid tyrosine phosphatase by benzofuran salicylic acids.
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DOI：
10.1021/jm101004d
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发表时间：
2011-01-27
影响因子：
7.3
通讯作者：
Tautz L
中科院分区：
文献类型：
--
作者：
Vang T;Xie Y;Liu WH;Vidović D;Liu Y;Wu S;Smith DH;Rinderspacher A;Chung C;Gong G;Mustelin T;Landry DW;Rickert RC;Schürer SC;Deng SX;Tautz L
The lymphoid tyrosine phosphatase (Lyp, PTPN22) is a critical negative regulator of T cell antigen receptor (TCR) signaling. A single-nucleotide polymorphism (SNP) in the ptpn22 gene correlates with the incidence of various autoimmune diseases, including type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus. Since the disease-associated allele is a more potent inhibitor of TCR signaling, specific Lyp inhibitors may become valuable in treating autoimmunity. Using a structure-based approach, we synthesized a library of 34 compounds that inhibited Lyp with IC50 values between 0.27 and 6.2 μM. A reporter assay was employed to screen for compounds that enhanced TCR signaling in cells, and several inhibitors displayed a dose-dependent, activating effect. Subsequent probing for Lyp's direct physiological targets by immunoblot analysis confirmed the ability of the compounds to inhibit Lyp in T cells. Selectivity profiling against closely related tyrosine phosphatases and in silico docking studies with the crystal structure of Lyp yielded valuable information for the design of Lyp-specific compounds.
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DOI：
10.1083/jcb.135.6.1515
发表时间：
1996-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Rodgers W;Rose JK
通讯作者：
Rose JK
影响因子：
16
作者：
Salmeen, A;Andersen, JN;Barford, D
通讯作者：
Barford, D
影响因子：
30.8
作者：
Vang, T;Congia, M;Bottini, N
通讯作者：
Bottini, N
影响因子：
3.6
作者：
Arimura, Yutaka;Vang, Torkel;Mustelin, Tomas
通讯作者：
Mustelin, Tomas
影响因子：
3.4
作者：
Wu, Shuangding;Bottini, Massimo;Rickert, Robert C.;Mustelin, Tomas;Tautz, Lutz
通讯作者：
Tautz, Lutz