학술논문
N-Succinyl-(β-alanyl-l -leucyl-l -alanyl-l -leucyl)doxorubicin: An Extracellularly Tumor-Activated Prodrug Devoid of Intravenous Acute Toxicity
Document Type
Article
Author
Source
Journal of Medicinal Chemistry; October 2001, Vol. 44 Issue: 22 p3750-3753, 4p
Subject
Language
ISSN
00222623; 15204804
Abstract
Intravenous administration of N-(β-alanyl-l -leucyl-l -alanyl-l -leucyl)doxorubicin (4 ) induces an acute toxic reaction, killing animals in a few minutes. This results from its positive charge at physiological pH combined with its propensity to form large aggregates in aqueous solutions. Negatively charged N-capped versions of 4 such as the succinyl derivative 5 can be administered by the iv route at more than 10 times the LD50 of doxorubicin without inducing the acute toxic reaction, and they are active in vivo.