title: A facile hydroxyindole carboxylic acid based focused library approach for potent and selective inhibitors of Mycobacterium protein tyrosine phosphatase B.
abstract: Focused on Mtb: A facile hydroxyindole carboxylic acid based focused amide library was designed to target both the PTP active site and a unique nearby pocket for enhanced affinity and selectivity. HTS of the library led to the identification of a highly potent and selective inhibitor, 11 a, of mPTPB, an essential virulence factor for Mycobacterium tuberculosis. Compound 11 a shows high cellular activity and is capable of reversing the altered immune responses induced by mPTPB in macrophages.
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Li-Fan
authors.initials: LF
authors.lastname: Zeng
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Yantao
authors.initials: Y
authors.lastname: He
authors.forename: Rongjun
authors.initials: R
authors.lastname: He
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Gunawan
authors.forename: Zhong-Yin
authors.initials: ZY
authors.lastname: Zhang
mesh_terms: D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D007211:Indoles; D054852:Small Molecule Libraries; D017027:Protein Tyrosine Phosphatases