Illudin S, a natural product isolated from mushrooms and various derivatives, have generally been demonstrated to possess several properties that make them unique as potential antitumor agents. In sensitive tumor cell types, illudin S has been shown to be a potent inhibitor of DNA synthesis that causes cell cycle arrest in S phase and retains antitumor activity against a broad range of drug-resistant tumor cell lines in vitro. Illudin S is also actively taken up by sensitive tumor cell types and damages the DNA in a unique manner that appears to require functional DNA helicase activity for DNA repair process to occur. MGI 114, 6-hydroxymethylacylfulvene (HMAF), is one of the analogs synthesized that was found to exhibit excellent in vitro and in vivo antitumor activity. Our hypothesis is that MGI 114, a synthetic derivative of the illudin S, has improved therapeutic margins and is believed to have potent effects on the synthesis of DNA that will cause the arrest in S phase. The primary objective of this study is to determine the maximum tolerated dose of MGI 114 administered intravenously once daily for five days every 28 days in patients with advanced cancer. Secondary objectives are to determine the toxicities associated with administration of MGI 114, determine the pharmacokinetics of MGI 114, and to determine the antitumor capabilities of MGI 114.
Showing the most recent 10 out of 459 publications
