1143579-84-3Relevant academic research and scientific papers
Discovery and evaluation of novel inhibitors of mycobacterium protein tyrosine phosphatase B from the 6-hydroxy-benzofuran-5-carboxylic acid scaffold
He, Yantao,Xu, Jie,Yu, Zhi-Hong,Gunawan, Andrea M.,Wu, Li,Wang, Lina,Zhang, Zhong-Yin
, p. 832 - 842 (2013)
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 n
A potent and selective small-molecule inhibitor for the lymphoid-specific tyrosine phosphatase (LYP), a target associated with autoimmune diseases
He, Yantao,Liu, Sijiu,Menon, Ambili,Stanford, Stephanie,Oppong, Emmanuel,Gunawan, Andrea M.,Wu, Li,Wu, Dennis J.,Barrios, Amy M.,Bottini, Nunzio,Cato, Andrew C. B.,Zhang, Zhong-Yin
, p. 4990 - 5008 (2013/07/26)
Lymphoid-specific tyrosine phosphatase (LYP), a member of the protein tyrosine phosphatase (PTP) family of signaling enzymes, is associated with a broad spectrum of autoimmune diseases. Herein we describe our structure-based lead optimization efforts with
TYROSINE PHOSPHATASE INHIBITORS AND USES THEREOF TO MODULATE THE ACTIVITY OF LYP
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Page/Page column title page; 45; 58; 62; 63; 81, (2012/11/13)
A variety of benzofurans and indole derivatives some with an acetyl linker are disclosed herein. These compounds are not highly charged at physiological pH and have good bioavailability characteristics. These compounds exhibit selective or at least preferential affinity for the active sites of various sub-sets of protein tyrosine phosphatases. The lymphoid- specific tyrosine phosphatase (Lyp) has received enormous attention because of the finding that a single- nucleotide polymorphism (SNP) in the gene (PTPN22) encoding Lyp is associated with several autoimmune diseases, including type I diabetes. Many of these compounds and pharmaceutically acceptable salts thereof are novel therapeutic compounds useful for the treatment of various diseases including a number of autoimmune diseases.
Targeting mycobacterium protein tyrosine phosphatase B for antituberculosis agents
Zhou, Bo,He, Yantao,Zhang, Xian,Xu, Jie,Luo, Yong,Wang, Yuehong,Franzblau, Scott G.,Yang, Zhenyun,Chan, Rebecca J.,Liu, Yan,Zheng, Jianyu,Zhang, Zhong-Yin
scheme or table, p. 4573 - 4578 (2010/10/03)
Protein tyrosine phosphatases are often exploited and subverted by pathogenic bacteria to cause human diseases. The tyrosine phosphatase mPTPB from Mycobacterium tuberculosis is an essential virulence factor that is secreted by the bacterium into the cytoplasm of macrophages, where it mediates mycobacterial survival in the host. Consequently, there is considerable interest in understanding the mechanism by which mPTPB evades the host immune responses, and in developing potent and selective mPTPB inhibitors as unique antituberculosis (antiTB) agents. We uncovered that mPTPB subverts the innate immune responses by blocking the ERK1/2 and p38 mediated IL-6 production and promoting host cell survival by activating the Akt pathway. We identified a potent and selective mPTPB inhibitor I-A09 with highly efficacious cellular activity, from a combinatorial library of bidentate benzofuran salicylic acid derivatives assembled by click chemistry. We demonstrated that inhibition of mPTPB with I-A09 in macrophages reverses the altered host immune responses induced by the bacterial phosphatase and prevents TB growth in host cells. The results provide the necessary proof-of-principle data to support the notion that specific inhibitors of the mPTPB may serve as effective antiTB therapeutics.
Derivatives of salicylic acid as inhibitors of YopH in yersinia pestis
Huang, Zunnan,He, Yantao,Zhang, Xian,Gunawan, Andrea,Wu, Li,Zhang, Zhong-Yin,Wong, Chung F.
scheme or table, p. 85 - 99 (2011/03/19)
Yersinia pestis causes diseases ranging from gastrointestinal syndromes to bubonic plague and could be misused as a biological weapon. As its protein tyrosine phosphatase YopH has already been demonstrated as a potential drug target, we have developed two series of forty salicylic acid derivatives and found sixteen to have micromolar inhibitory activity. We designed these ligands to have two chemical moieties connected by a flexible hydrocarbon linker to target two pockets in the active site of the protein to achieve binding affinity and selectivity. One moiety possessed the salicylic acid core intending to target the phosphotyrosine-binding pocket. The other moiety contained different chemical fragments meant to target a nearby secondary pocket. The two series of compounds differed by having hydrocarbon linkers with different lengths. Before experimental co-crystal structures are available, we have performed molecular docking to predict how these compounds might bind to the protein and to generate structural models for performing binding affinity calculation to aid future optimization of these series of compounds.
