HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Antitumor activity and toxicity in animals of BMY-25282, a new mitomycin derivative.

Abstract
BMY-25282, 7-N-(dimethylamino methylene)mitomycin C, is one of a novel series of amidino mitomycin derivatives. Some of these were discovered as intermediates in a synthetic program being conducted to find improved procedures for modifying the structure of mitomycin C (MMC). Markedly superior in vivo antitumor effects have been observed with BMY-25282 compared to MMC in initial tests against i.p.-implanted P388 leukemia and B16 melanoma. When administered i.v. to mice bearing s.c. B16 melanoma, BMY-25282 was also superior to MMC. The derivative was fully active against a line of L1210 leukemia which was partially resistant to MMC treatment but had little or no activity against a line of L1210 fully resistant to MMC. It is also 2 to 4 times more potent than MMC based on a comparison of doses required to achieve optimum antitumor effects. The superior antitumor efficacy of BMY-25282 over MMC against both i.p. and s.c. B16 melanoma was maintained when the drug was given in pluronic acid formulation. Against P-388 leukemia, however, the efficacy of the drugs was equivalent when BMY-25282 was administered in the pluronic vehicle. In an in vitro clonogenic assay involving freshly explanted human tumors, BMY-25282 was consistently more potent in cytotoxic effects than MMC. With human colorectal carcinoma samples, BMY-25282 was 13.8 times more potent than MMC. The i.v. 50% lethal dose values of BMY-25282 and MMC in C57BL/6 X DBA/2 F1 mice were 2.1 mg/kg and 8.6 mg/kg, respectively. Leukopenic effects of the drugs in mice were comparable at doses up to their respective 50% lethal dose values. Hematology studies in ferrets revealed a similar pattern of depression and recovery of lymphocytes, neutrophils, and platelets for BMY-25282 and MMC; however, with BMY-25282 there was earlier recovery of platelet counts. BMY-25282 is being further developed toward possible clinical trial.
AuthorsW T Bradner, W C Rose, J E Schurig, A P Florczyk, J B Huftalen, J J Catino
JournalCancer research (Cancer Res) Vol. 45 Issue 12 Pt 1 Pg. 6475-81 (Dec 1985) ISSN: 0008-5472 [Print] United States
PMID3933826 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Mitomycins
  • Mitomycin
  • N(6)-((dimethylamino)methylene)mitomycin C
Topics
  • Animals
  • Blood Cell Count (drug effects)
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Female
  • Ferrets
  • Leukemia, Experimental (drug therapy)
  • Leukocyte Count (drug effects)
  • Male
  • Mice
  • Mitomycin
  • Mitomycins (therapeutic use, toxicity)
  • Neoplastic Stem Cells (drug effects)
  • Structure-Activity Relationship

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: