A new inhibitor of protein kinase C, RK-286C (4'-demethylamino-4'-hydroxystaurosporine). I. Screening, taxonomy, fermentation and biological activity.
In the course of our screening program using a bleb-forming assay, a new inhibitor of protein kinase C (PKC) was found in the fermentation of a streptomycete. The inhibitor, RK-286C (4'-demethylamino-4'-hydroxystaurosporine), inhibited the morphological change of K562 cells, a human chronic erythroleukemia cell, induced by phorbol 12,13-dibutylate at the concentration of 3 microM. The same concentration of the compound inhibited the activity of PKC in vitro and the aggregation of rabbit platelets induced by collagen and arachidonic acid.
Osada
H
H
Antibiotics Laboratory, RIKEN, Institute of Physical and Chemical Research, Saitama, Japan.
Takahashi
H
H
Tsunoda
K
K
Kusakabe
H
H
Isono
K
K
D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D004354:Drug Screening Assays, Antitumor; D005285:Fermentation; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011817:Rabbits; D019311:Staurosporine / Q000031:analogs & derivatives; D013302:Streptomyces / Q000378:metabolism
D000470:Alkaloids; D000900:Anti-Bacterial Agents; D010975:Platelet Aggregation Inhibitors; C063438:4'-demethylamino-4'-hydroxystaurosporine; D011493:Protein Kinase C; D019311:Staurosporine