Dendreon Presents Preclinical Data Demonstrating Activity of TRPM8 Agonist, D-3263, in Benign Prostatic Hyperplasia
– Data Presented at American Urological Association Annual Meeting –
The abstract (#1408), “Preclinical Evaluation of the TRPM8 Ion Channel Agonist D-3263 for Benign Prostatic Hyperplasia” is being presented at the American Urological Association’s (AUA) 2009 Annual Meeting in
In a preclinical study, BPH was induced in rats through subcutaneous injection of testosterone propionate (TP). One week after initiation of BPH, either D-3263, finasteride (an inhibitor of the enzyme 5-alpha-reductase) or a combination of the two agents was administered daily for two weeks. Following treatment, blood was sampled, prostates were collected and weighed, and tissue sections were examined histologically.
Rats with TP-induced BPH who were treated with D-3263, finasteride or a combination of the two, had a significant reduction (p=0.004) of mean prostate weight and prostate hyperplasia with evidence of a dose response. In addition, the highest dose of D-3263 given in combination with finasteride resulted in lower prostate weights than either agent given alone, suggesting a potential additive effect. BPH-induced animals showed increases in dihydrotestosterone (DHT) concentrations in the plasma, levels of which were reduced in animals treated with D-3263, finasteride or a combination of the two. While finasteride is a known inhibitor of 5-alpha reductase, the enzyme that converts testosterone to DHT, D-3263 is not an inhibitor of this enzyme suggesting that the two agents may act by different means to affect androgen metabolism and prostate hyperplasia.
“BPH is a condition that affects a significant number of men, and based on the preclinical data announced today demonstrating the drug’s ability to reduce the size and weight of the prostate, we believe that D-3263 may be able to impact this disease,” said
TRPM8 (also known as TRPP8) was identified through Dendreon’s in-house discovery efforts. It is an ion channel that is triggered by cold temperatures and small-molecule agonists and belongs to the melastatin subfamily – one of seven subfamilies of TRP proteins. In normal human tissues, TRPM8 is expressed predominantly in the prostate, a gland in the male reproductive system. It is over-expressed in prostate hyperplasia and multiple types of cancer including prostate cancer, breast cancer, colon cancer and lung cancer. In recent years, it has emerged that TRP channels play a diverse and key role in cell biology and in pathology. Dendreon has synthesized small molecule agonists including D3263 that activate the TRPM8 ion channel and induce cell death.
Dendreon Corporation is a biotechnology company whose mission is to target cancer and transform lives through the discovery, development and commercialization of novel therapeutics. The Company applies its expertise in antigen identification, engineering and cell processing to produce active cellular immunotherapy product candidates designed to stimulate an immune response. Dendreon is also developing an orally-available small molecule that targets TRPM8 that could be applicable to multiple types of cancer as well as BPH. The Company has its headquarters in
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