title: Synthesis of a tetronic acid library focused on inhibitors of tyrosine and dual-specificity protein phosphatases and its evaluation regarding VHR and cdc25B inhibition.
abstract: Selective inhibitors of protein tyrosine phosphatases (PTPs) and dual-specificity phosphatases (DSPs) are expected to be useful tools for clarifying the biological functions of the PTPs themselves and also to be candidates for novel therapeutics. We planned a library approach for the identification of PTP/DSP inhibitors in which 3-acyltetronic acid is used as a "core" phosphate mimic. A series of novel tetronic acid derivatives were synthesized and evaluated as inhibitors of the dual-specificity protein phosphatases VHR and cdc25B. Several compounds are found to be potent inhibitors of cdc25B, which is a key enzyme for cell-cycle progression. The promising results described herein strongly indicated that this tetronic acid library is potent as a library focused on the PTP/DSP-selective inhibitor.
authors.affiliation: Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba, Sendai 980-8577, Japan. sodeoka@tagen.tohoku.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Sodeoka
authors.forename: R
authors.initials: R
authors.lastname: Sampe
authors.forename: S
authors.initials: S
authors.lastname: Kojima
authors.forename: Y
authors.initials: Y
authors.lastname: Baba
authors.forename: T
authors.initials: T
authors.lastname: Usui
authors.forename: K
authors.initials: K
authors.lastname: Ueda
authors.forename: H
authors.initials: H
authors.lastname: Osada
mesh_terms: D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D020650:Combinatorial Chemistry Techniques; D054640:Dual Specificity Phosphatase 3; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D004926:Escherichia coli / Q000378:metabolism; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D020687:cdc25 Phosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D005663:Furans; D054640:Dual Specificity Phosphatase 3; D017027:Protein Tyrosine Phosphatases; D020687:cdc25 Phosphatases; C003422:tetronic acid