title: Isolation of a novel tyrosine kinase inhibitor, lavendustin A, from Streptomyces griseolavendus.
abstract: A potent tyrosine kinase inhibitor, lavendustin A [1], has been isolated from a butyl acetate extract of Streptomyces griseolavendus culture filtrate. It inhibits epidermal growth factor receptor-associated tyrosine kinase with an IC50 of 4.4 ng/ml, which is about 50 times more inhibitory than erbstatin. It does not inhibit protein kinase A or C. Its structure, determined by spectral data and total synthesis, is novel, having a tertiary amine in the center with substituted benzyl and phenyl groups. Lavendustin A competes with ATP and is noncompetitive with the peptide. Its structure-activity relationship is discussed.
authors.affiliation: Institute of Microbial Chemistry, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Onoda
authors.forename: H
authors.initials: H
authors.lastname: Iinuma
authors.forename: Y
authors.initials: Y
authors.lastname: Sasaki
authors.forename: M
authors.initials: M
authors.lastname: Hamada
authors.forename: K
authors.initials: K
authors.lastname: Isshiki
authors.forename: H
authors.initials: H
authors.lastname: Naganawa
authors.forename: T
authors.initials: T
authors.lastname: Takeuchi
authors.forename: K
authors.initials: K
authors.lastname: Tatsuta
authors.forename: K
authors.initials: K
authors.lastname: Umezawa
mesh_terms: D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010636:Phenols / Q000302:isolation & purification / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013302:Streptomyces / Q000032:analysis*
chemical_list: D010636:Phenols; C062898:lavendustin A; D011505:Protein-Tyrosine Kinases