Biomaterial Database

Toxicological study on a new nitrosourea derivative, 1-(2-chloroethyl)-3-isobutyl-3-(beta-maltosyl)-1-nitrosourea. 1985

S Fujimoto, and M Ogawa

TA-077, 1-(2-chloroethyl)-3-isobutyl-3-(beta-maltosyl)-1-nitrosourea, is a new water-soluble nitrosourea derivative which is disubstituted at the N-3 position of the structure, and is activated by a unique mechanism whereby organic isocyanates can never be produced. In order to clarify the biological functions of the organic isocyanates which common nitrosourea derivatives generate, TA-077 was tested in BDF1 mice for lethality, weight loss and hematological toxicity. TA-077 showed qualitatively and quantitatively similar toxicity to other nitrosourea derivatives which generate organic isocyanates, such as 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosour ea (ACNU), methyl 6-[3-(2-chloroethyl)-3-nitrosoureido ]-6-deoxy-alpha-D-glucopyranoside (MCNU), and 1-(2-chloroethyl)-3-(beta-D-glucopyranosyl)-1-nitrosourea (GANU), indicating that the organic isocyanates do not play an important role in the biological activity of the nitrosourea derivatives. Furthermore, the toxicity of TA-077 did not increase significantly (except for weight loss) when the drug was administered daily for five days, and TA-077 given according to this schedule showed far more effective antitumor activity than when given as a single treatment. These results suggested that TA-077 is an analog suitable for consecutive administration in cancer treatment.

UI	MeSH Term	Description	Entries
D007970	Leukopenia	A decrease in the number of LEUKOCYTES in a blood sample below the normal range (LEUKOCYTE COUNT less than 4000).	Leukocytopenia,Leukocytopenias,Leukopenias
D008815	Mice, Inbred Strains	Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.	Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D009607	Nitrosourea Compounds	A class of compounds in which the core molecule is R-NO, where R is UREA.	Compounds, Nitrosourea
D001835	Body Weight	The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.	Body Weights,Weight, Body,Weights, Body
D004334	Drug Administration Schedule	Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.	Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D005260	Female		Females
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013997	Time Factors	Elements of limited time intervals, contributing to particular results or situations.	Time Series,Factor, Time,Time Factor
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus