Identification and Characterization of Novel Inhibitors of mPTPB, an Essential Virulent Phosphatase from Mycobacterium tuberculosis
作者： Lan Chen , Bo Zhou , Sheng Zhang , Li Wu , Yuehong Wang
DOI: 10.1021/ML1001135
关键词:
摘要: Mycobacterium protein tyrosine phosphatase B (mPTPB) is an essential virulence factor required for tuberculosis (Mtb) survival in host macrophages. Consequently, mPTPB represents exciting new target with a completely novel mechanism of action. We screened library 7500 compounds against and identified several 2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide piperazinyl-thiophenyl-ethyl-oxalamide derivatives as two distinct classes inhibitors. showed that both inhibitors are capable blocking the mPTPB-mediated ERK1/2 inactivation. further demonstrated effective inhibiting growth Mtb Thus, improvement lead may produce class anti-TB agents.
acs.org
sci-hub.se 参考文章(13)
Declan Butler, New fronts in an old war Nature. ,vol. 406, pp. 670- 672 ,(2000) , 10.1038/35021291
Daniela Müller, Anja Krick, Stefan Kehraus, Christian Mehner, Mark Hart, Frithjof C. Küpper, Krishna Saxena, Heino Prinz, Harald Schwalbe, Petra Janning, Herbert Waldmann, Gabriele M. König, Brunsvicamides A−C: Sponge-Related Cyanobacterial Peptides with Mycobacterium tuberculosis Protein Tyrosine Phosphatase Inhibitory Activity Journal of Medicinal Chemistry. ,vol. 49, pp. 4871- 4878 ,(2006) , 10.1021/JM060327W
Christoph Grundner, Dominique Perrin, Rob Hooft van Huijsduijnen, Dominique Swinnen, Jérome Gonzalez, Christine L. Gee, Timothy N. Wells, Tom Alber, Structural Basis for Selective Inhibition of Mycobacterium tuberculosis Protein Tyrosine Phosphatase PtpB. Structure. ,vol. 15, pp. 499- 509 ,(2007) , 10.1016/J.STR.2007.03.003
Lay Pheng Tan, Hao Wu, Peng-Yu Yang, Karunakaran A. Kalesh, Xiaohua Zhang, Mingyu Hu, Rajavel Srinivasan, Shao Q. Yao, High-Throughput Discovery of Mycobacterium tuberculosis Protein Tyrosine Phosphatase B (MptpB) Inhibitors Using Click Chemistry Organic Letters. ,vol. 11, pp. 5102- 5105 ,(2009) , 10.1021/OL9023419
Matthew B. Soellner, Katherine A. Rawls, Christoph Grundner, Tom Alber, Jonathan A. Ellman, Fragment-based substrate activity screening method for the identification of potent inhibitors of the Mycobacterium tuberculosis phosphatase PtpB. Journal of the American Chemical Society. ,vol. 129, pp. 9613- 9615 ,(2007) , 10.1021/JA0727520
Zhong-Yin Zhang, Protein tyrosine phosphatases: prospects for therapeutics. Current Opinion in Chemical Biology. ,vol. 5, pp. 416- 423 ,(2001) , 10.1016/S1367-5931(00)00223-4
Anil Koul, Thomas Herget, Bert Klebl, Axel Ullrich, Interplay between mycobacteria and host signalling pathways. Nature Reviews Microbiology. ,vol. 2, pp. 189- 202 ,(2004) , 10.1038/NRMICRO840
Anne E Clatworthy, Emily Pierson, Deborah T Hung, Targeting virulence: a new paradigm for antimicrobial therapy Nature Chemical Biology. ,vol. 3, pp. 541- 548 ,(2007) , 10.1038/NCHEMBIO.2007.24
Nicola J. Beresford, Debbie Mulhearn, Bruce Szczepankiewicz, Gang Liu, Michael E. Johnson, Anthony Fordham-Skelton, Cele Abad-Zapatero, Jennifer S. Cavet, Lydia Tabernero, Inhibition of MptpB phosphatase from Mycobacterium tuberculosis impairs mycobacterial survival in macrophages Journal of Antimicrobial Chemotherapy. ,vol. 63, pp. 928- 936 ,(2009) , 10.1093/JAC/DKP031
Kanakeshwari Falzari, Zhaohai Zhu, Dahua Pan, Huiwen Liu, Poonpilas Hongmanee, Scott G. Franzblau, In Vitro and In Vivo Activities of Macrolide Derivatives against Mycobacterium tuberculosis Antimicrobial Agents and Chemotherapy. ,vol. 49, pp. 1447- 1454 ,(2005) , 10.1128/AAC.49.4.1447-1454.2005