Furamidine Found to Inhibit a Key Enzyme Involved in Cancer Cell DNA Repair Mechanisms
NEW YORK, Aug. 14 /PRNewswire-FirstCall/ -- Immtech Pharmaceuticals, Inc. (Amex: IMM) commented today on a recent paper published in Nucleic Acids Research by a group of researchers at the National Cancer Institute on the ability of furamidine to inhibit a key enzyme involved in the DNA repair process (see Note below). Furamidine is the active metabolite (DB75) of Immtech's proprietary, orally bioavailable prodrug, pafuramidine. Of interest is furamidine's potential to inhibit DNA repair in cancerous cells that have been damaged by chemotherapy agents. Furamidine may thus synergistically and selectively enhance the antiproliferative effects of the classes of anticancer agents known as topoisomerase 1 or 2 (Top1, Top2) inhibitors.
This paper highlights a new high-throughput assay for evaluating potential tyrosyl-DNA phosphodiesterase (Tdp1) inhibitors and the activity of furamidine as a low micromolar inhibitor of the enzyme. Furamidine was one of the most potent compounds to come from screening a set comprising of 1981 compounds. The screening was part of the NCI-Development Therapeutics Program.
The authors note that functionally, Tdp1 is part of the DNA repair complex that resolves the irreversible Top1-DNA cleavage complexes by catalyzing the hydrolysis of 3'-phosphotyrolsyl bonds. They further suggest that a Tdp1 inhibitor could act synergistically with the Top1 inhibitors. Earlier work implicates Tdp1 in the repair of Top2-mediated DNA damage. Top2 inhibitors represent another class of anticancer agents where a Tdp1 inhibitor may produce a synergistic response.
Eric L. Sorkin, Immtech's Chairman and Chief Executive Officer, stated, 'We commend the authors for their efforts. At Immtech, we too continue to explore expanding the potential applications of our dications for novel therapeutic uses.'
Note: Smitha Antony et al., Oxford Journals, June 18, 2007, 'Novel high- throughput electrochemiluminescent assay for identification of human tyrosyl- DNA phosphodiesterase (Tdp1) inhibitors and characterization of furamidine (NSC305831) as an inhibitor of Tdp1,' Nucleic Acids Research, http://nar.oxfordjournals.org/,
Copyright (C) 2007 Oxford University Press.