PTP1B in complex with a phosphonic acid inhibitor
[PTN1_HUMAN] Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion. 
Publication Abstract from PubMed
A series of quinoline/naphthalene-difluoromethylphosphonates were prepared and were found to be potent PTP1B inhibitors. Most of these compounds bearing polar functionalities or large lipophilic residues did not show appreciable oral bioavailability in rodents while small and less polar analogs displayed moderate to good oral bioavailability. The title compound was found to have the best overall potency and pharmacokinetic profile and was found to be efficacious in animal models of diabetes and cancer.
Discovery of [(3-bromo-7-cyano-2-naphthyl)(difluoro)methyl]phosphonic acid, a potent and orally active small molecule PTP1B inhibitor.,Han Y, Belley M, Bayly CI, Colucci J, Dufresne C, Giroux A, Lau CK, Leblanc Y, McKay D, Therien M, Wilson MC, Skorey K, Chan CC, Scapin G, Kennedy BP Bioorg Med Chem Lett. 2008 Jun 1;18(11):3200-5. Epub 2008 Apr 29. PMID:18477508
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.