Preclinical pharmacokinetic, toxicological and biomarker evaluation of SR16157, a novel dual-acting steroid sulfatase inhibitor and selective estrogen receptor modulator

摘要

Purpose SR16157 is a novel dual-acting inhibitor of estrogen action that irreversibly inhibits the estrogen biosynthetic enzyme steroid sulfatase (STS) and releases the selective estrogen receptor modulator SR16137, which blocks the estrogen receptor. SR16157 is a promising agent for the endocrine therapy of breast cancer. We conducted preclinical in vivo toxicity evaluations to determine the maximum-tolerated dose (MTD), target organ(s) of toxicity, reversibility, dose-limiting toxicity, no observable adverse effect level (NOAEL), and toxicokinetics (TK) and to investigate a potential biomarker for use in SR16157 clinical trials.