N-Succinyl-(beta-alanyl-L-leucyl-L-alanyl-L-leucyl)doxorubicin: an extracellularly tumor-activated prodrug devoid of intravenous acute toxicity
| Autor: | Luc Dasnois, André Trouet, E R Lewis, Karim Lebtahi, K. Van Derpoorten, T J Lobl, Vincent Dubois, Anne-Marie Fernandez, D Shochat, S Gangwar, Cecilia Oliyai |
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| Rok vydání: | 2001 |
| Předmět: |
Male
medicine.medical_specialty Ultrafiltration Peptide Antineoplastic Agents Pharmacology Lethal Dose 50 Mice Drug Stability In vivo Internal medicine Drug Discovery medicine Toxicity Tests Acute Tumor Cells Cultured Animals Humans Doxorubicin Prodrugs Chromatography High Pressure Liquid chemistry.chemical_classification Mice Inbred BALB C Tetrapeptide Chemistry Biological activity Prodrug Xenograft Model Antitumor Assays Acute toxicity Solutions Endocrinology Toxicity Injections Intravenous bacteria Molecular Medicine Female Oligopeptides Injections Intraperitoneal medicine.drug |
| Zdroj: | Journal of medicinal chemistry. 44(22) |
| ISSN: | 0022-2623 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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