NEW YORK, April 16 /PRNewswire/ -- NexGenix Pharmaceuticals, presented data on its Hsp90 inhibitor program today at the Annual Meeting of the AACR in San Diego today. The company presented data in the experimental therapeutics session on NXD30001, one of several novel, radicicol-based Hsp90 inhibitors in its compound series.
NXD30001 demonstrated efficacy in breast cancer tumor xenograft models without evidence for liver and kidney toxicity. The potency, tolerability, pharmacokinetic and pharmacodynamic properties of NXD30001 and its derivatives indicate that it, or an analog, may be useful in the treatment of breast and other forms of cancer with an improved dosing and therapeutic window compared to 17AAG, the first-in-class Hsp90 inhibitor currently in Phase 2 clinical trials for cancer.
The compound series appears to bind Hsp90 in a different mode than 17AAG or radicicol and exhibit higher affinity to Hsp90 than radicicol. NXD30001 and its analogs efficiently inhibit cell proliferation and deplete multiple Hsp90 client proteins such as Her2, Akt, c-Raf, Cdk4, and Cyclin D1 in Her2-overexpressing breast and other cancer cell lines at low nanomolar concentrations. Pharmacokinetic studies demonstrate that NXD30001 can achieve potential therapeutic levels via intraperitoneal (i.p.) dosing and that the compound accumulates in tumors at above micromolar concentrations.
Tumor pharmacodynamic analysis demonstrated depletion of multiple Hsp90 client proteins, including Her2, after a single dose; these client proteins remained undetectable for more than 2 days, consistent with the pharmacokinetic tumor data.
"A number of analogs with activity similar to or better than NXD30001
have been synthesized and are being evaluated for oral bioavailability,
tolerability, and efficacy," stated Allan Rubenstein, MD, CEO of NexGenix.
"Our intent is to progress an i.v. formulation of NXD30001 into
IND-enabling studies for breast cancer, and to develop
|SOURCE NexGenix Pharmaceuticals|
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