Potent homophthalimide-type inhibitors of B16F10/L5 mouse melanoma cell invasion.
Recently, we developed a series of novel and potent aminopeptidase inhibitors with a homophthalimide skeleton. Among them, N-(2,6-diethylphenyl)homophthalimide (PIQ-22) possesses a specific aminopeptidase-inhibiting activity more potent than that of bestatin or actinonin, as assayed in terms of hydrolysis of L-alanine 4-methylcoumaryl-7-amide (Ala-AMC) by human acute lymphoblastic leukemia MOLT-4 cells. We show here that PIQ-22 and its 2,6-dimethylphenyl derivative (PIQ-11) are more potent inhibitors of tumor cell invasion than bestatin and actinonin in a Matrigel assay using mouse melanoma B16F10/L5 cells.
Kagechika
H
H
Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan.
Komoda
M
M
Fujimoto
Y
Y
Koiso
Y
Y
Takayama
H
H
Kadoya
S
S
Miyata
K
K
Kato
F
F
Kato
M
M
Hashimoto
Y
Y
D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology* / Q000627:therapeutic use; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008546:Melanoma, Experimental; D051379:Mice; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D007546:Isoquinolines; C400282:N-(2,6-diethylphenyl)homophthalimide; C400281:N-(2,6-dimethylphenyl)homophthalimide; D000626:Aminopeptidases; D007930:Leucine; C012211:ubenimex; C010531:actinonin