Monamidocin, a novel fibrinogen receptor antagonist. II. Biological activity and structure-activity relationships.
Monamidocin, a fibrinogen receptor binding inhibitor produced by Streptomyces sp. NR 0637, inhibits the binding of fibrinogen to its receptor with an IC50 of 0.21 microM. It also inhibits ADP-collagen- and thrombin-induced aggregation of human platelet with IC50S of 46, 30, and 77 microM, respectively. To obtain more potent inhibitors, twenty analogs have been synthesized, among which N-[(R)-5-guanidino-2-hydroxypentanoyl]-L-tyrosine is the most potent. It inhibits the binding of fibrinogen to its receptors with an IC50 of 0.022 microM and is about ten times more potent than monamidocin.
Kamiyama
T
T
Nippon Roche Research Center, Kamakura, Japan.
Satoh
T
T
Umino
T
T
Katoh
H
H
Uemura
F
F
Nakamura
Y
Y
Yokose
K
K
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000595:Amino Acid Sequence; D003094:Collagen / Q000494:pharmacology; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013302:Streptomyces / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology
C097816:N-(5-guanidino-2-hydroxypentanoyl)tyrosine; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C097815:monamidocin; D014443:Tyrosine; D010649:Phenylalanine; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D003094:Collagen; D013917:Thrombin