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Isolation of a novel substrate‐competitive tyrosine kinase inhibitor, desmal, from the plant Desmos chinensis
Author(s) -
Kakeya Hideaki,
Imoto Masaya,
Tabata Yuji,
Iwami Junko,
Matsumoto Haruhiko,
Nakamura Kazuo,
Koyano Takashi,
Tadano Kin-ichi,
Umezawa Kazuo
Publication year - 1993
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(93)80085-9
Subject(s) - biochemistry , substrate (aquarium) , tyrosine kinase , enzyme , chemistry , size exclusion chromatography , receptor tyrosine kinase , epidermal growth factor , inositol , kinase , receptor , biology , ecology
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 (ER 12) cells. It also inhibited EGF‐induced inositol phosphate formation and morphological changes.