title: Calix[4]arene methylenebisphosphonic acids as inhibitors of protein tyrosine phosphatase 1B.
abstract: Сalix[4]arenes bearing methylenebisphosphonic or hydroxymethylenebisphosphonic acid fragments at the wide rim of the macrocycle were studied as inhibitors of PTP1B. Some of the inhibitors showed IC50 values in the micromolar range and good selectivity in comparison with other protein tyrosine phosphatases such as TC-PTP, PTPβ, LAR, and CD45. Kinetic studies indicated that the calix[4]arene derivatives influence PTP1B activity as slow-binding inhibitors. Based on molecular docking results, the binding modes of the macrocyclic bisphosphonates in the active centre of PTP1B are discussed.
authors.affiliation: Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, Murmanska, 1, 02660 Kyiv-94, Ukraine.
authors.forename: Viacheslav V
authors.initials: VV
authors.lastname: Trush
authors.forename: Sergiy O
authors.initials: SO
authors.lastname: Cherenok
authors.forename: Vsevolod Yu
authors.initials: VY
authors.lastname: Tanchuk
authors.forename: Valery P
authors.initials: VP
authors.lastname: Kukhar
authors.forename: Vitaly I
authors.initials: VI
authors.lastname: Kalchenko
authors.forename: Andriy I
authors.initials: AI
authors.lastname: Vovk
mesh_terms: D001665:Binding Sites; D047250:Calixarenes / Q000737:chemistry*; D004164:Diphosphonates / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D062105:Molecular Docking Simulation; D010636:Phenols / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004164:Diphosphonates; D004791:Enzyme Inhibitors; D010636:Phenols; C121325:calix(4)arene; D047250:Calixarenes; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
keywords: Calixarene; Inhibition; Methylenebisphosphonic acid; Molecular docking; Protein tyrosine phosphatase 1B