Isolation of a novel substrate-competitive tyrosine kinase inhibitor, desmal, from the plant Desmos chinensis.
In the course of a screening program for tyrosine kinase inhibitors, the chloroform extract of a tropical plant, Desmos chinensis, strongly inhibited the enzyme activity. The active substance was purified by silica gel, gel filtration, and finally crystallized. The structure was elucidated by mass spectrometry and X-ray crystallography to be 8-formyl-2,5,7-trihydroxy-6- methylflavanone, and we named it desmal. Desmal competed with peptide substrate and non-competed with ATP. It inhibited tyrosine kinase in situ in epidermal growth factor (EGF) receptor-overexpressing NIH3T3 (ER12) cells. It also inhibited EGF-induced inositol phosphate formation and morphological changes.
Kakeya
H
H
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.
Imoto
M
M
Tabata
Y
Y
Iwami
J
J
Matsumoto
H
H
Nakamura
K
K
Koyano
T
T
Tadano
K
K
Umezawa
K
K
D016475:3T3 Cells; D000818:Animals; D003599:Cytoskeleton / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D044950:Flavanones; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D010944:Plants / Q000737:chemistry*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D014443:Tyrosine / Q000378:metabolism; D014961:X-Ray Diffraction
D044950:Flavanones; D005419:Flavonoids; D007295:Inositol Phosphates; C080424:desmal; D014443:Tyrosine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases