title: RK-682, a potent inhibitor of tyrosine phosphatase, arrested the mammalian cell cycle progression at G1phase.
abstract: A specific inhibitor of protein tyrosine phosphatase (PTPase), RK-682 (3-hexadecanoyl-5-hydroxymethyl-tetronic acid) was isolated from microbial metabolites. In vitro, RK-682 inhibited dephosphorylation activity of CD45 and VHR with IC50 54 and 2.0 microM, respectively. In situ, sodium orthovanadate and RK-682 enhanced the phosphotyrosine level of Ball-1 cells, a human B cell leukemia, but not the phosphoserine/threonine level. The PTPase inhibitors, however, had the different arrest point on the cell cycle progression. Sodium orthovanadate inhibited the cell cycle progression at G2/M boundary phase, on the other hand, RK-682 inhibited the G1/S transition.
authors.affiliation: Antibiotics Laboratory, Institute of Physical and Chemical Research (RIKEN), Saitama, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hamaguchi
authors.forename: T
authors.initials: T
authors.lastname: Sudo
authors.forename: H
authors.initials: H
authors.lastname: Osada
mesh_terms: D000814:Aniline Compounds / Q000378:metabolism; D000935:Antifungal Agents / Q000494:pharmacology; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors*; D054640:Dual Specificity Phosphatase 3; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000494:pharmacology; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D015448:Leukemia, B-Cell; D019319:Okadaic Acid; D009943:Organophosphorus Compounds / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism; D019000:Phosphotyrosine / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D011714:Pyrans; D013141:Spiro Compounds; D013302:Streptomyces / Q000737:chemistry; D014407:Tumor Cells, Cultured; D014638:Vanadates / Q000494:pharmacology; D020687:cdc25 Phosphatases
chemical_list: D000814:Aniline Compounds; D000935:Antifungal Agents; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D004988:Ethers, Cyclic; D009943:Organophosphorus Compounds; D010750:Phosphoproteins; D011714:Pyrans; C094097:RK 682; D013141:Spiro Compounds; C053079:tautomycin; D019319:Okadaic Acid; D019000:Phosphotyrosine; D014638:Vanadates; C068798:4-aminophenylphosphate; D010749:Phosphoprotein Phosphatases; C517025:DUSP3 protein, human; D054640:Dual Specificity Phosphatase 3; D017027:Protein Tyrosine Phosphatases; D020687:cdc25 Phosphatases