title: Isolation of a novel protein tyrosine phosphatase inhibitor, 2-methyl-fervenulone, and its precursors from Streptomyces.
abstract: High-throughput screening identified an extract from Streptomyces sp. IM 2096 with inhibitory activity toward several protein tyrosine phosphatases (PTPs). Four 1,2,4-triazine compounds 2096A-D (1-4) were isolated from this extract and their structures elucidated by interpretation of spectroscopic data and confirmed by degradation and synthesis. The novel glycocyamidine derivatives 1 and 2 are diastereomers and may interconvert. Both are inactive in the PTP inhibition assay. Compounds 1 and 2 are unstable and partially decompose to 3 and glycocyamidine (5) at room temperature. Compound 3, known as MSD-92 or 2-methyl-fervenulone, is a broad-specificity PTP inhibitor with comparable potency to vanadate. The imidazo[4, 5-e]-1,2,4-triazine (4), inactive in the PTP-inhibition assay, may be a degradation product of 3.
authors.affiliation: Medicinal and Combinatorial Chemistry Laboratory, Cell Regulation Laboratory, Lead Discovery Group, Microbial Collection and Screening Laboratory, Singapore.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: K L
authors.initials: KL
authors.lastname: Lim
authors.forename: S L
authors.initials: SL
authors.lastname: Yeo
authors.forename: X
authors.initials: X
authors.lastname: Xu
authors.forename: M M
authors.initials: MM
authors.lastname: Sim
authors.forename: A E
authors.initials: AE
authors.lastname: Ting
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Yee
authors.forename: Y H
authors.initials: YH
authors.lastname: Tan
authors.forename: C J
authors.initials: CJ
authors.lastname: Pallen
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D015394:Molecular Structure; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D013057:Spectrum Analysis; D013302:Streptomyces / Q000201:enzymology*; D014227:Triazines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
chemical_list: C421034:2-methyl-fervenulone; D004791:Enzyme Inhibitors; D014227:Triazines; D017027:Protein Tyrosine Phosphatases