A novel metal-chelating inhibitor of protein farnesyltransferase.
A novel metal chelator comprising a 4-(naphthalen-1-yl)pyridine and 2-aminoethanethiol was synthesized. This showed inhibitory activity against human protein farnesyltransferase with IC(50) 1.9 microM, induced morphological change in K-ras-NRK cells at 0.5 microg/mL and showed growth inhibition of K-ras-NRK cells with IC(50) 0.32 microg/mL.
Hamasaki
Akiyuki
A
Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
Naka
Hayato
H
Tamanoi
Fuyuhiko
F
Umezawa
Kazuo
K
Otsuka
Masami
M
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002712:Chlorides / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011905:Genes, ras / Q000187:drug effects; D006801:Humans; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D017967:Zinc Compounds / Q000737:chemistry
D002614:Chelating Agents; D002712:Chlorides; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D011725:Pyridines; D017967:Zinc Compounds; C016837:zinc chloride; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase