Isolation of a novel tyrosine kinase inhibitor, lavendustin A, from Streptomyces griseolavendus.
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.
Onoda
T
T
Institute of Microbial Chemistry, Tokyo, Japan.
Iinuma
H
H
Sasaki
Y
Y
Hamada
M
M
Isshiki
K
K
Naganawa
H
H
Takeuchi
T
T
Tatsuta
K
K
Umezawa
K
K
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*
D010636:Phenols; C062898:lavendustin A; D011505:Protein-Tyrosine Kinases