Sporostatin, a novel and specific inhibitor of EGF receptor kinase.
Sporostatin isolated from a fungus of Sporormiella sp.M5032 as an inhibitor of cyclic adenosine 3',5'-monophosphate phosphodiesterase, was found to be a specific inhibitor of epidermal growth factor (EGF) receptor tyrosine kinase in vitro. Its IC50 values were 0.1 microgram/ml (0.38 microM) for EGF receptor kinase, 3 micrograms/ml (11 microM) for ErbB-2, and 100 micrograms/ml (380 microM) or more than that for other kinases including PDGF receptor, v-src and protein kinase C. Kinetic analyses revealed that inhibition of EGF receptor kinase by sporostatin was noncompetitive either with substrate or with ATP. Autophosphorylation of EGF receptor in A431 cells was also inhibited. These results show that sporostatin is a potent and specific inhibitor of EGF receptor kinase.
Murakami
Y
Y
Department of Bioactive Molecules, National Institute of Infectious Diseases, Tokyo, Japan.
Ishii
A
A
Mizuno
S
S
Yaginuma
S
S
Uehara
Y
Y
D000804:Angiotensin II / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D018942:Macrolides / Q000494:pharmacology*; D010766:Phosphorylation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000804:Angiotensin II; D004791:Enzyme Inhibitors; D066246:ErbB Receptors; D018942:Macrolides; D018719:Erb-b2 Receptor Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor; C112275:sporostatin