Single-dose pharmacokinetic and toxicity analysis of pyrrole-imidazole polyamides in mice.

ABSTRACT:

Purpose

Pyrrole-imidazole (Py-Im) polyamides are programmable, sequence-specific DNA minor groove-binding ligands. Previous work in cell culture has shown that various polyamides can be used to modulate the transcriptional programs of oncogenic transcription factors. In this study, two hairpin polyamides with demonstrated activity against androgen receptor signaling in cell culture were administered to mice to characterize their pharmacokinetic properties.

Methods

Py-Im polyamides were administered intravenously by tail vein injection. Plasma, urine, and fecal samples were collected over a 24-h period. Liver, kidney, and lung samples were collected postmortem. Concentrations of the administered polyamide in the plasma, excretion, and tissue samples were measured using LC/MS/

SUBMITTER: Synold TW 

PROVIDER: S-EPMC3456924 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature