Antitumor activity of ethyl 5-amino-1,2-dihydro-2-methyl-3-phenyl-pyrido [3,4-b]pyrazin-7-ylcarbamate, 2-hydroxyethanesulfonate, hydrate (NSC 370147) against selected tumor systems in culture and in mice.
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| Abstract |
Ethyl 5-amino-1,2-dihydro-2-methyl-3-phenylpyrido[3,4-b]pyrazin- 7-ylcarbamate, 2-hydroxyethanesulfonate, hydrate (NSC 370147) was evaluated for antitumor activity against a spectrum of tumor systems in culture and in mice. NSC 370147 was cytotoxic to a variety of mouse and human cell lines at nanomolar concentrations. The compound exhibited good in vivo antitumor activity against several murine tumors (P388 and L1210 leukemia, colon 11/A and 36, mammary 16/C, and M5076 sarcoma). Activity was largely independent of route of administration but favored a prolonged treatment schedule. NSC 370147 was as active against murine leukemia sublines resistant to Adriamycin, amsacrine, vincristine, melphalan, cisplatin, methotrexate, and CI-920 (a topoisomerase II inhibitor) as against the corresponding parental lines. Only the 1-beta-D-arabinofuranosylcytosine-resistant P388 subline exhibited any cross-resistance to NSC 370147. NSC 370147 has a spectrum of activity similar to that of vincristine and, unlike vincristine, is active against multidrug-resistant cell lines. Therefore, NSC 370147 is a candidate for clinical trial because of its favorable activity compared to vincristine, its effectiveness against multidrug-resistant cells, and its retention of activity for p.o. administration.
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| Authors | W R Waud, W R Leopold, W L Elliott, D J Dykes, W R Laster Jr, C G Temple Jr, S D Harrison Jr, D P Griswold Jr |
| Journal | Cancer research (Cancer Res) Vol. 50 Issue 11 Pg. 3239-44 (Jun 01 1990) ISSN: 0008-5472 [Print] United States |
| PMID | 2334919 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.) |
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