Potent and specific inhibitors of protein kinase C of microbial origin.
Potent and specific inhibitors of protein kinase C have been found in streptomyces and fungi: Staurosporine, an alkaloid from Streptomyces sp., is the most potent inhibitor of protein kinases with an IC50 in the nanomolar range. UCN-01 (7-hydroxy staurosporine), isolated from Streptomyces sp., is a selective inhibitor of protein kinase C with antitumor activity. Calphostin, isolated from the fungus Cladosporium cladosporioides, specifically inhibits protein kinase C (IC50 = 0.05 microM) without inhibiting other protein kinases. Microbial metabolites appear to be a promising source of inhibitors that target signal transduction pathways of eukaryotes.
Kyowa Hakko Co. Ltd., Tokyo Research Laboratories, Japan.
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D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology; D001419:Bacteria / Q000032:analysis*; D002227:Carbazoles / Q000302:isolation & purification / Q000494:pharmacology; D005658:Fungi / Q000032:analysis*; D026121:Indole Alkaloids; D009281:Naphthalenes; D010766:Phosphorylation; D011083:Polycyclic Compounds / Q000302:isolation & purification / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine / Q000031:analogs & derivatives
D000470:Alkaloids; D002227:Carbazoles; D026121:Indole Alkaloids; D009281:Naphthalenes; D011083:Polycyclic Compounds; C061465:calphostin complex; C054852:7-hydroxystaurosporine; C049985:staurosporine aglycone; D011493:Protein Kinase C; D019311:Staurosporine