title: Discovery of a novel competitive inhibitor of PTP1B by high-throughput screening.
abstract: OBJECTIVE
  The aim of the present study was to discover novel protein tyrosine phosphatase 1B (PTP1B) inhibitors. We expressed and purified the human PTP1B catalytic domain and set up a molecular level high-throughput screening (HTS) assay to screen a set of 48,000 pure compounds.
  
  
  RESULTS
  HTS was finished with an averaged Zo factor of 0.63, and LGH00081, a competitive inhibitor of PTP1B with novel structure and relatively good selectivity for receptor-type protein tyrosine phosphatases, was identified.
  
  
  CONCLUSIONS
  We established a molecular level assay which is useful for the screening of PTP1B inhibitors with therapeutic potential. The novel competitive PTP1B inhibitor LGH00081 offers a good start for structure modification and cellular functional activity study.
authors.affiliation: National Center for Drug Screening, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Hai-ping
authors.initials: HP
authors.lastname: Yu
authors.forename: Yue-yang
authors.initials: YY
authors.lastname: Zhou
authors.forename: Jun-qin
authors.initials: JQ
authors.lastname: Du
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shen
authors.forename: Jing-ya
authors.initials: JY
authors.lastname: Li
authors.forename: Jia
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D016466:CHO Cells; D002384:Catalysis; D006224:Cricetinae; D003412:Cricetulus; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D010766:Phosphorylation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D014443:Tyrosine / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D014443:Tyrosine; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1