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Biotech / Medical : Biotech Valuation -- Ignore unavailable to you. Want to Upgrade?

To: scaram(o)uche who wrote (178)	4/22/1999 2:00:00 PM
From: Biomaven	Read Replies (1) \| Respond to of 52153

Here's the title of the one ASCO abstract I could find: "9-Nitro-20- (S)-Camptothecin (9-NC, RFS2000): An Effective Agent for Treatment of Chronic Myelomonocytic Leukemia (CMML) and Philadelphia Chromosome (Ph)-Negative Chronic Myelogenous Leukemia (CML)" -------------------------------------------------------------------------------- General Poster Session: Leukemia and Myelodysplasia Date: "May 17, 1999" Time: 1:00 PM - 5:00 PM Location: Hall C (East Wing) And from AACR: PROC. AMER. ASSOC. CANCER RES. 40, March 1999] Copyright © 1999 by the American Association for Cancer Research #717 Intrinsic anticancer activity of 9-nitrocamptothecin (9NC or RFS 2000) compared to 9-aminocamptothecin. Liehr, Joachim G., Mendoza, J., Harris, N., Giovanella, B.C., Burke, T.G. Stehlin Foundation for Cancer Res., Houston, TX 77003 and University of Kentucky College of Pharmacy, Lexington, KY 40506. 9-Nitrocamptothecin (9NC or RFS 2000) is a potent anticancer agent that has demonstrated efficacy in a large Phase II trial in pancreatic cancer. In addition, antitumor activity has been seen in refractory ovarian cancer, myelodysplastic syndrome, and in a wide variety of tumors including breast, lung and colorectal. In the past, it has been suggested that the anticancer activity of 9-nitrocamptothecin may be related to its bioconversion to 9-aminocamptothecin (9AC) because 9AC is a potent anticancer agent in nude mice and because this metabolic process has been detected (<6%) in human cells in culture and in humans and laboratory animals in vivo. As part of our examination of the mechanism of anticancer action of 9NC, we studied the inhibition of topoisomerase I activity by 9NC and compared it to that of 9AC and of the parent compound camptothecin. Supercoiled plasmid DNA incubated with enzyme, forms a cleavable complex of short half-life unless it is stabilized by enzyme inhibitors. In this system, both 9NC and 9AC (50-500 µM) stabilized the cleavable complex, whereas at least 100 µM camptothecin were needed for a comparable effect. Our data demonstrate that 9NC is a powerful inhibitor of topoisomerase I. We conclude that the anticancer activity of 9NC is based on the intrinsic topoisomerase I-inhibiting activity of this drug and is not dependent on its conversion to 9AC. Supported by funds of SuperGen, Inc. Peter