Small-molecule therapy for metastatic prostate cancer

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Enzalutamide resistance is a major obstacle in the treatment of metastatic, castration-resistant prostate cancer (mCRPC). Recently we developed a small-molecule lead compound GH501 and demonstrated its potent activity against bone metastatic prostate cancer cells. In this Phase I STTR application, we hypothesize that GH501 is a novel lead compound with nanomolar potency against enzalutamide-resistant and bone metastatic prostate cancer. Two Aims are proposed. In Aim 1, we will synthesize high-purity GH501 and determine the acute toxicity, pharmacokinetics and in vivo bioavailability/distribution of GH501 in rodent models; in Aim 2, we will validate the in vivo efficacy of GH501 against mCRPC in clinically-relevant animal models. These studies will provide convincing rationale for us to continue the GH501 project at MetCure for further pre-clinical and clinical development. The project has important impact and translational potential in treating a lethal disease.