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Japanese Journal of Cancer Research :... Oct 1997A novel quinoline derivative, TAS-103 (6-[[2-(dimethylamino)ethyl]amino]-3-hydroxy-7H-indeno[2,1-c]quinolin -7-one dihydrochloride), was developed as an anticancer agent...
A novel quinoline derivative, TAS-103 (6-[[2-(dimethylamino)ethyl]amino]-3-hydroxy-7H-indeno[2,1-c]quinolin -7-one dihydrochloride), was developed as an anticancer agent targeting topoisomerases (topo) I and II, with marked efficacy in solid tumors. TAS-103 inhibited topo I and II (IC50: 2 microM, 6.5 microM) at a concentration similar to or lower than those of previous agents, and had a strong cytotoxic effect on P388 and KB cells (IC50: 0.0011 microM, 0.0096 microM). TAS-103 stabilized topo I and II-DNA cleavable complexes in KB cells, generating a similar amount of topo II-DNA complex to that induced by etoposide (VP-16) but a smaller amount of topo I-DNA complex than that produced by camptothecin (CPT). In the in vivo study, intermittent i.v. administration was markedly effective against s.c.-implanted murine tumors. Furthermore, TAS-103 had marked efficacy against various lung metastatic tumors, and a broad antitumor spectrum in human tumor xenografts (derived from lung, colon, stomach, breast, and pancreatic cancer). The efficacy of TAS-103 was generally greater than that of irinotecan (CPT-11), VP-16, or cis-diamminedichloroplatinum (CDDP).
Topics: Adenocarcinoma; Aminoquinolines; Animals; Antineoplastic Agents; Camptothecin; Cisplatin; Colonic Neoplasms; DNA; DNA Topoisomerases, Type I; DNA Topoisomerases, Type II; Dose-Response Relationship, Drug; Etoposide; Humans; Indenes; Indoles; Irinotecan; Lung Neoplasms; Male; Melanoma; Mice; Mice, Inbred Strains; Neoplasm Transplantation; Neoplasms, Experimental; Pyridines; Topoisomerase I Inhibitors; Topoisomerase II Inhibitors; Tumor Cells, Cultured
PubMed: 9414662
DOI: 10.1111/j.1349-7006.1997.tb00320.x