AF prodrug

Molecular structure of AF prodrug.

Aminoflavone (NSC 686288)

1996 Aminoflavone (NSC 686288) is a synthetic material that is related to compounds found in plants called flavonoids, which modulate various biological activities. In 1996, aminoflavone (AF) was received by DTP for screening.

1997 In the human tumor cell line in vitro screen, both AF and the AF prodrug (NSC 710464) have demonstrated antiproliferative activity against several renal, breast, and ovarian cancer cell lines. Of particular interest, AF produced a unique COMPARE pattern of activity with no statistically significant correlation to patterns of activity of known classes of antitumor agents.1 A unique pattern of activity for a new agent in this screen is consistent with a novel mechanism of drug action.

2002 Based on good activity against renal (four out of six animals were tumor-free in a CaKi-1 model) and breast tumors in animal studies, the AF prodrug was presented and accepted by DDG in 2002. DTP conducted pharmacokinetic studies and IND-directed toxicology studies on this agent.2 In light of the promising results of preclinical studies and an acceptable toxicity profile, the decision was made to initiate NCI-sponsored clinical trials of the DTP-produced AF prodrug.

2005 The Cancer Therapy Evaluation Program (CTEP) of NCI expects to file an investigational new drug (IND) application with the FDA for AF prodrug before the end of 2005.2

1 Kuffel MJ, Schroeder JC, Pobst LJ, Naylor S, Reid JM, Kaufmann SH, Ames MM. Activation of the antitumor agent aminoflavone (NSC 686288) is mediated by induction of tumor cell cytochrome P450 1A1/1A2. Mol Pharmacol 2002;62:143–153.

2 NIH Office of Technology Transfer. Technology abstracts: aminoflavone prodrug.

3 National Cancer Institute. New drug for renal cancer to enter phase I trials. NCI Cancer Bulletin 1994;1:3.

DTP aminoflavone/Phortress go-no go poster (pdf)

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“That aminoflavone worked in renal tumor explants, which are closer to tumors in people than cell cultures, is promising…This means AF may kill tumor cells without destroying bone marrow and having other toxic effects…Those tumor cells that metabolized the drug—which included a number of papillary renal cell arcinoma—self-destructed.”

—Dr. Edward Sausville, former Associate Director of DTP3

 National Cancer Institute National Institutes of Heatlh Department of Health and Human Services FirstGov  






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