Discovery of small-molecule inhibitors of the TLR1/TLR2 complex.

Discovery of small-molecule inhibitors of the TLR1/TLR2 complex.
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DOI:
10.1002/anie.201204910
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发表时间:
2012-12-03
影响因子:
16.6
通讯作者:
Yin, Hang
Yin, Hang
中科院分区:
化学1区
文献类型:
--
作者:
Cheng, Kui;Wang, Xiaohui;Zhang, Shuting;Yin, Hang

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Toll样受体1和2(TLR 1/2)的蛋白复合物是先天免疫的重要调节因子,因此为治疗各种免疫疾病提供了有吸引力的靶点。在这里,我们报告了一种新的化合物(CU-CPT 22),它可以与合成的三酰化脂蛋白(Pam 3CSK 4)竞争结合TLR 1/2,具有高抑制活性和特异性。还观察到TNF-α和IL-1β的下游信号传导受到抑制。
The protein complex of toll-like receptor 1 and 2 (TLR1/2) is an important regulator of innate immunity, and therefore provides an attractive target for the treatment of various immune disordres. Here we report a novel compound (CU-CPT22) that can compete with the synthetic triacylated lipoprotein (Pam3CSK4) binding to TLR1/2 with high inhibitory activity and specificity. Repression of downstream signaling from TNF-α and IL-1β has also been observed.
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