119706-03-5Relevant academic research and scientific papers
Salicylic acid based small molecule inhibitor for the oncogenic src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2)
Zhang, Xian,He, Yantao,Liu, Sijiu,Yu, Zhihong,Jiang, Zhong-Xing,Yang, Zhenyun,Dong, Yuanshu,Nabinger, Sarah C.,Wu, Li,Gunawan, Andrea M.,Wang, Lina,Chan, Rebecca J.,Zhang, Zhong-Yin
experimental part, p. 2482 - 2493 (2010/09/03)
The Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) plays a pivotal role in growth factor and cytokine signaling. Gain-of-function SHP2 mutations are associated with Noonan syndrome, various kinds of leukemias, and solid tumors. Thus, there is considerable interest in SHP2 as a potential target for anticancer and antileukemia therapy. We report a salicylic acid based combinatorial library approach aimed at binding both active site and unique nearby subpockets for enhanced affinity and selectivity. Screening of the library led to the identification of a SHP2 inhibitor II-B08 (compound 9) with highly efficacious cellular activity. Compound 9 blocks growth factor stimulated ERK1/2 activation and hematopoietic progenitor proliferation, providing supporting evidence that chemical inhibition of SHP2 may be therapeutically useful for anticancer and antileukemia treatment. X-ray crystallographic analysis of the structure of SHP2 in complex with 9 reveals molecular determinants that can be exploited for the acquisition of more potent and selective SHP2 inhibitors.
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.
IMIDAZOLE DERIVATIVES USED AS TAFIA INHIBITORS
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, (2008/06/13)
The present invention relates to compounds of formula (I) which are inhibitors of the activated thrombin-activatable fibrinolysis inhibitor. The compounds of formula (I) are suited for producing medicaments for the prevention and treatment of diseases acc
IMIDAZOLE DERIVATIVES USED AS TAFIA INHIBITORS
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Page/Page column 59, (2010/02/14)
The invention relates to compounds of formula (I), which are inhibitors of the activated thrombin-activatable fibrinolysis inhibitor. The compounds of formula (I) are suited for producing medicaments for the prevention and treatment of diseases accompanied by thromboses, embolisms, hypercoagulability or fibrotic changes.
A potent and highly selective inhibitor of human α-1,3-fucosyltransferase via click chemistry
Lee, Lac V.,Mitchell, Michael L.,Huang, Shih-Jung,Fokin, Valery V.,Sharpless, K. Barry,Wong, Chi-Huey
, p. 9588 - 9589 (2007/10/03)
Potent inhibitors of fucosyltransferases, and glycosyltransferases in general, have been elusive due to the inherent barriers surrounding the family of glycosyltransfer reactions. The problems of weak substrate affinity and low catalytic proficiency of fu
N-BENZHYDRYL-GLYCOLAMIDE ESTERS (OBg ESTERS) AS CARBOXYL PROTECTING GROUPS IN PEPTIDE SYNTHESIS
Amblard, Muriel,Rodriguez, Marc,Martinez, Jean
, p. 5101 - 5108 (2007/10/02)
N-benzhydryl-glycolamide esters (OBg esters) of various N-protected amino acids have been synthesized.In order to demonstrate their usefulness in peptide chemistry, the syntheses of For-Met-Leu-Phe-OH (chemiotactic peptide) and Pro-Leu-Gly-NH2 (MIF) have been carried out.OBg esters are compatible with commonly used protecting groups and are cleanly and selectively removed in mild alkaline conditions without any side reaction, except for β-benzyl aspartyl containing sequences.
