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.

Public Health Relevance

In this Phase I STTR application, we will develop a potent small-molecule drug GH501 to overcome enzalutamide resistance and treat bone metastatic prostate cancer, a major cause of cancer death in American men. This project has important impact in treating a lethal disease, reducing cancer morbidity and improving healthcare in the United States and globally.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Technology Transfer (STTR) Grants - Phase I (R41)
Project #
1R41CA217491-01A1
Application #
9407585
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Weber, Patricia A
Project Start
2017-08-01
Project End
2019-07-31
Budget Start
2017-08-01
Budget End
2019-07-31
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Metcure Therapeutics, LLC
Department
Type
DUNS #
078866511
City
Atlanta
State
GA
Country
United States
Zip Code
30341