858004-74-7Relevant academic research and scientific papers
Cefsulodin Inspired Potent and Selective Inhibitors of mPTPB, a Virulent Phosphatase from Mycobacterium tuberculosis
He, Rongjun,Yu, Zhi-Hong,Zhang, Ruo-Yu,Wu, Li,Gunawan, Andrea M.,Zhang, Zhong-Yin
, p. 1231 - 1235 (2015)
mPTPB is a virulent phosphatase from Mycobacterium tuberculosis and a promising therapeutic target for tuberculosis. To facilitate mPTPB-based drug discovery, we identified α-sulfophenylacetic amide (SPAA) from cefsulodin, a third generation β-lactam ceph
Inhibition of Low Molecular Weight Protein Tyrosine Phosphatase by an Induced-Fit Mechanism
He, Rongjun,Wang, Jifeng,Yu, Zhi-Hong,Zhang, Ruo-Yu,Liu, Sijiu,Wu, Li,Zhang, Zhong-Yin
, p. 9094 - 9106 (2016)
The low molecular weight protein tyrosine phosphatase (LMW-PTP) is a regulator of a number of signaling pathways and has been implicated as a potential target for oncology and diabetes/obesity. There is significant therapeutic interest in developing potent and selective inhibitors to control LMW-PTP activity. We report the discovery of a novel class of LMW-PTP inhibitors derived from sulfophenyl acetic amide (SPAA), some of which exhibit greater than 50-fold preference for LMW-PTP over a large panel of PTPs. X-ray crystallography reveals that binding of SPAA-based inhibitors induces a striking conformational change in the LMW-PTP active site, leading to the formation of a previously undisclosed hydrophobic pocket to accommodate the α-phenyl ring in the ligand. This induced-fit mechanism is likely a major contributor responsible for the exquisite inhibitor selectivity.
