Activity of datelliptium acetate (NSC 311152; SR 95156A) against solid tumors of mice.
Datelliptium acetate (NSC 311152) is a water soluble analogue of ellipticine. It is a solid tumor selective compound. In vitro, in a disk diffusion, soft agar colony formation assay (25 micrograms/disk), the compound demonstrated solid tumor selectivity (compared to leukemia L1210) against colon adenocarcinoma 38 and pancreas ductal carcinoma 03. Upon intravenous administration, NSC 311152 was effective in vivo against a variety of murine solid tumors. Responses at maximum tolerated doses were: colon #07/A (T/C = 33%); 0.60 log cell kill), #38 [T/C = 0%; 4.2 log cell kill), colon #51/A (T/C = 2%; 1.2 log cell kill), undifferentiated colon #26/A (T/C = 38%; 0.4 log kill), mammary #16/C (T/C = 10%; 1.7 log cell kill), and pancreatic ductal carcinoma #03 (T/C = 0%; 80% cures through day 38). It was ineffective against pancreas #02 (T/C = 45%), mammary 17/A (T/C = 53%), and 17/A/ADR (T/C = 52%). At efficacious doses acute neurotoxicity (i.e. stupor and lethargy) and weight loss were noted (with rapid recovery from both toxicities). There were no delayed toxicities. The agent was slightly necrotizing and produced pain on SC injections. In lieu of its preclinical efficacy and toxicity profiles, we recommend further clinical investigation of this agent.
Mucci-LoRusso
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P
Department of Medicine, Wayne State University School of Medicine, Detroit, MI 48201.
Polin
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L
Biernat
L A
LA
Valeriote
F A
FA
Corbett
T H
TH
D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy; D003110:Colonic Neoplasms / Q000188:drug therapy; D004354:Drug Screening Assays, Antitumor; D004611:Ellipticines / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007939:Leukemia L1210 / Q000188:drug therapy; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D010190:Pancreatic Neoplasms / Q000188:drug therapy
D004611:Ellipticines; C060073:detalliptinium