Fragment Screening and Assembly: A Highly Efficient Approach to a Selective and Cell Active Protein Tyrosine Phosphatase 1B Inhibitor
Gang Liu(Abbott Fund), Zhili Xin(Abbott Fund), Zhonghua Pei(Abbott Fund), Philip J. Hajduk(Abbott Fund), Cele Abad‐Zapatero(Abbott Fund), Charles W. Hutchins(Abbott Fund), Hongyu Zhao(Abbott Fund), Thomas Lübben(Abbott Fund), Stephen J. Ballaron(Abbott Fund), Deanna L. Haasch(Abbott Fund), Wiweka Kaszubska(Abbott Fund), Cristina M. Rondinone(Abbott Fund), James M. Trevillyan(Abbott Fund), Michael R. Jirousek(Abbott Fund)
Cited by 163Open Access
Abstract
Using an NMR-based fragment screening and X-ray crystal structure-based assembly, starting with millimolar ligands for both the catalytic site and the second phosphotyrosine binding site, we have identified a small-molecule inhibitor of protein tyrosine phosphatase 1B with low micromolar inhibition constant, high selectivity (30-fold) over the highly homologous T-cell protein tyrosine phosphatase, and good cellular activity in COS-7 cells.
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