caa a22 4500 465789692 CHVBK 20180323112020.0 cr unu---uuuuu 170327e19900301xx s 000 0 eng 10.1007/BF00171978 doi (NATIONALLICENCE)springer-10.1007/BF00171978 Antitumor activity and toxicity in animals of N-7[2-(4-nitrophenyidithio) ethyl] mitomycin C (BMY-25067) [Elektronische Daten] [William Bradner, William Rose, John Schurig, Alexander Florczyk] Summary: BMY-25067, N-7[2-(4-nitrophenyldithio)-ethyl] mitomycin C was selected from a number of disulfide derivatives of the highly active compound RR150, N-7(thioethyl) mitomycin C for further study. BMY-25067 had tumor inhibitory effects equivalent to mitomycin C (MMC) against ascitic P388 and L1210 leukemias and M109 lung carcinoma in mice with i.p. treatment. However, it demonstrated superior activity against B16 melanoma with a high percentage of cures when both tumors and drug were given i.p. Additionally, in separate tests against B16 melanoma implanted s.c. with treatment i.V., BMY-25067 was also consistently superior to MMC. This activity was observed when therapy was initiated either one day post-tumor implant or delayed until the ninth day post-tumor implant. Slight activity was seen against a line of L1210 partially resistant to MMC and none against a line of P388 completely resistant to MMC. Against s.c. M109, BMY-25067 inhibited tumor growth but did not prolong survival with the treatment schedule used. At their respective maximum non-lethal doses in mice, BMY-25067 was less neutropenic than MMC. This was confirmed in ferrets which were also examined for the compound's effects on platelets. BMY-25067 appeared to have much less effect on platelets than MMC; the nadir for BMY-25067 was 3.8 × 105 platelets/ cmm compared to 7 × 104 platelets/cmm for MMC when the drugs were compared at a dose ratio of 2:1, BMY-25067:MMC (determined to represent their relative potencies). This initial evidence of superior antitumor effectiveness particularly to a solid tumor separated from site of treatment and reduced hematologic toxicity suggest that BMY-25067 may be a worthwhile candidate for clinical trial. Kluwer Academic Publishers, 1990 mitomycin C derivative nationallicence therapeutic efficacy nationallicence toxicity nationallicence BMY-25067 nationallicence Bradner William Pharmaceutical Research and Development Division, Bristol-Myers Company, P.O. Box 4755, 13221-4755, Syracuse, New York, USA aut Rose William Pharmaceutical Research and Development Division, Bristol-Myers Company, P.O. Box 4755, 13221-4755, Syracuse, New York, USA aut Schurig John Pharmaceutical Research and Development Division, Bristol-Myers Company, P.O. Box 4755, 13221-4755, Syracuse, New York, USA aut Florczyk Alexander Pharmaceutical Research and Development Division, Bristol-Myers Company, P.O. Box 4755, 13221-4755, Syracuse, New York, USA aut Investigational New Drugs Kluwer Academic Publishers 8(1990-03-01), S1-S7 0167-6997 8<S1 1990 8 10637 https://doi.org/10.1007/BF00171978 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00171978 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Bradner William Pharmaceutical Research and Development Division, Bristol-Myers Company, P.O. Box 4755, 13221-4755, Syracuse, New York, USA aut NATIONALLICENCE 700 1- Rose William Pharmaceutical Research and Development Division, Bristol-Myers Company, P.O. Box 4755, 13221-4755, Syracuse, New York, USA aut NATIONALLICENCE 700 1- Schurig John Pharmaceutical Research and Development Division, Bristol-Myers Company, P.O. Box 4755, 13221-4755, Syracuse, New York, USA aut NATIONALLICENCE 700 1- Florczyk Alexander Pharmaceutical Research and Development Division, Bristol-Myers Company, P.O. Box 4755, 13221-4755, Syracuse, New York, USA aut NATIONALLICENCE 773 0- Investigational New Drugs Kluwer Academic Publishers 8(1990-03-01), S1-S7 0167-6997 8<S1 1990 8 10637 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer