In vivo evidence of complete circumvention of vincristine resistance by a new triazinoaminopiperidine derivative S 9788 in P388/VCR leukemia model.
S 9788, a new triazinoaminopiperidine derivative, was found to be a potent reversant of vincristine resistance in the in vivo murine leukemic P388/VCR model. In two treatment regimens (Q4D days 1, 5 and 9 and QD days 1-9), S 9788 enhanced the antitumor activity of vincristine in a dose-dependent manner, resulting in a complete circumvention of drug resistance for well-tolerated doses of S 9788. S 9788 was also effective in enhancing therapeutic effects of vincristine in the treatment of sensitive P388-bearing mice. These results strongly suggest that S 9788 may be a potential candidate for circumvention of multidrug resistance (MDR) in clinical practice.
Cros
S
S
C.N.R.S., Laboratoire de Pharmacologie et Toxicologie Fondamentales, Toulouse, France.
Guilbaud
N
N
Berlion
M
M
Dunn
T
T
Regnier
G
G
Dhainaut
A
A
Atassi
G
G
Bizzari
J P
JP
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D007941:Leukemia P388 / Q000188:drug therapy* / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D014227:Triazines / Q000008:administration & dosage / Q000494:pharmacology*; D014750:Vincristine / Q000008:administration & dosage / Q000627:therapeutic use*
D010880:Piperidines; D014227:Triazines; C077022:S 9788; D014750:Vincristine