The discovery of novel tartrate-based TNF-alpha converting enzyme (TACE) inhibitors

发现新型酒石酸类 TNF-α 转换酶 (TACE) 抑制剂

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作者:Kristin E Rosner, Zhuyan Guo, Peter Orth, Gerald W Shipps Jr, David B Belanger, Tin Yau Chan, Patrick J Curran, Chaoyang Dai, Yongqi Deng, Vinay M Girijavallabhan, Liwu Hong, Brian J Lavey, Joe F Lee, Dansu Li, Zhidan Liu, Janeta Popovici-Muller, Pauline C Ting, Henry Vaccaro, Li Wang, Tong Wang, We

Abstract

A novel series of TNF-alpha convertase (TACE) inhibitors which are non-hydroxamate have been discovered. These compounds are bis-amides of L-tartaric acid (tartrate) and coordinate to the active site zinc in a tridentate manner. They are selective for TACE over other MMP's. We report the first X-ray crystal structure for a tartrate-based TACE inhibitor.

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