Calphostin C (UCN-1028C), a novel microbial compound, is a highly potent and specific inhibitor of protein kinase C.
Calphostin C (UCN-1028C), a newly isolated compound from Cladosporium cladosporioides, is a potent and specific inhibitor of protein kinase C, because it was 1000 times more inhibitory to protein kinase C (IC50, 0.05 microM) than other protein kinases such as cAMP-dependent protein kinase and tyrosine-specific protein kinase (IC50, greater than 50 microM). Calphostin C did not inhibit calcium activated neutral protease (calpain)-digested protein kinase C, indicating that it interacts with the regulatory domain of protein kinase C. In addition this compound showed inhibitory effects on the binding of [3H]PDBu to protein kinase C. The potent cytotoxic activity and antitumor activity of calphostin C might be due to the inhibition of protein kinase C, and thus it may be potentially useful for the therapeutic application.
Kobayashi
E
E
Tokyo Research Laboratories, Kyowa Hakko Kogyo Co. Ltd., Japan.
Nakano
H
H
Morimoto
M
M
Tamaoki
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D002455:Cell Division / Q000187:drug effects; D002963:Cladosporium / Q000032:analysis*; D005656:Fungal Proteins / Q000494:pharmacology*; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D003904:Mitosporic Fungi / Q000032:analysis*; D009281:Naphthalenes; D010703:Phorbol Esters / Q000378:metabolism; D011083:Polycyclic Compounds / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D011955:Receptors, Drug / Q000187:drug effects
D000970:Antineoplastic Agents; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D005656:Fungal Proteins; D009281:Naphthalenes; D010703:Phorbol Esters; D011083:Polycyclic Compounds; D011955:Receptors, Drug; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; D011493:Protein Kinase C; C058819:calphostin C