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N-Succinyl-(beta-alanyl-L-leucyl-L-alanyl-L-leucyl)doxorubicin: an extracellularly tumor-activated prodrug devoid of intravenous acute toxicity.

Abstract：

:Intravenous administration of N-(beta-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 LD(50) of doxorubicin without inducing the acute toxic reaction, and they are active in vivo.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Fernandez AM,Van Derpoorten K,Dasnois L,Lebtahi K,Dubois V,Lobl TJ,Gangwar S,Oliyai C,Lewis ER,Shochat D,Trouet A

doi

10.1021/jm0108754

keywords:

subject

Has Abstract

pub_date

2001-10-25 00:00:00

pages

3750-3

issue

22

eissn

0022-2623

issn

1520-4804

pii

jm0108754

journal_volume

44

pub_type

杂志文章

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