AI Article Synopsis
- HE3235 (Apoptone) is a synthetic drug designed to target prostate and breast cancer, currently in Phase IIa trials for prostate cancer treatment.
- Preclinical studies assessed how HE3235 interacts with nuclear hormone receptors and enzymes, showing promising safety and effective metabolite profiles in various animal models.
- Safety studies on rats and dogs highlighted a good safety margin for human use, although certain side effects like anorexia and hypokalemia could occur at higher doses.
Article Abstract
17α-ethynyl-5α-androstane-3α, 17β-diol (HE3235, Apoptone) is an orally bioavailable synthetic analogue of 3β-androstanediol, that is active in rodent models of prostate and breast cancer, and is in Phase IIa clinical trials for the treatment of early- and late-stage prostate cancer. In preparation for clinical studies, nuclear hormone receptor and P450 interactions for HE3235 and major metabolites were characterized in vitro, and pharmacokinetics and metabolite profiles were studied in rodents, dogs, and monkeys. Four-week safety studies conducted in rats and dogs indicated a substantial margin of safety for clinical use, and no evidence of electrocardiographic or neurological effects, although anorexia, thrombocytopenia, and hypokalemia were identified as potentially dose-limiting toxicities at superpharmacological exposures. Pharmacokinetics and drug metabolism have been studied in prostate cancer patients.
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| http://dx.doi.org/10.1007/s10637-010-9517-0 | DOI Listing |
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