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Updated: May 26, 2026
An Ex vivo Model to Study Hormone Action in the Human Breast
Published on: January 8, 2015
Targeting human progesterone receptor (PR), through pharmacophore-based screening and molecular simulation revealed
Muhammad Shahab1, Peng Ziyu2, Muhammad Waqas3
1State Key Laboratories of Chemical Resources Engineering, Beijing University of Chemical Technology, Beijing, 100029, People's Republic of China.
Abstract:
Breast cancer, the prevailing malignant tumor among women, is linked to progesterone and its receptor (PR) in both tumorigenesis and treatment responsiveness. Despite thorough investigation, the precise molecular mechanisms of progesterone in breast cancer remain unclear. The human progesterone receptor (PR) serves as an essential therapeutic target for breast cancer treatment, warranting the rapid design of small molecule therapeutics that can effectively inhibit HPR. By employing cutting-edge computational techniques like molecular screening, simulation, and free energy calculation, the process of identifying potential lead molecules from natural products has been significantly expedited. In this study, we employed pharmacophore-based virtual screening and molecular simulations to identify natural product-based inhibitors of human progesterone receptor (PR) in breast cancer treatment. High-throughput molecular screening of traditional Chinese medicine (TCM) and zinc databases was performed, leading to the identification of potential lead compounds. The analysis of binding modes for the top five compounds from both database provides valuable structural insights into the inhibition of HPR for breast cancer treatment. The top five hits exhibited enhanced stability and compactness compared to the reference compound. In conclusion, our study provides valuable insights for identifying and refining lead compounds as HPR inhibitors.
Insights
Researchers identified natural compounds that may inhibit the human progesterone receptor (HPR), a key target in breast cancer treatment. This discovery aids in developing new small molecule therapeutics for breast cancer.
Area of Science:
- Oncology
- Pharmacology
- Computational Chemistry
Background:
- Breast cancer is the most common cancer in women, with progesterone and its receptor (PR) playing roles in its development and treatment response.
- The exact molecular mechanisms of progesterone in breast cancer are not fully understood.
- Inhibiting the human progesterone receptor (HPR) is a crucial therapeutic strategy for breast cancer.
Purpose of the Study:
- To identify natural product-based inhibitors of the human progesterone receptor (HPR) for breast cancer treatment.
- To expedite the design of small molecule therapeutics targeting HPR.
Main Methods:
- Utilized pharmacophore-based virtual screening and molecular simulations.
- Performed high-throughput molecular screening of traditional Chinese medicine (TCM) and zinc databases.
- Analyzed binding modes of top identified compounds.
Main Results:
- Identified potential lead compounds from TCM and zinc databases.
- Top five compounds showed enhanced stability and compactness compared to the reference.
- Structural insights into HPR inhibition were gained from binding mode analysis.
Conclusions:
- The study provides valuable insights for identifying and refining lead compounds as HPR inhibitors.
- This research supports the development of novel breast cancer therapeutics targeting HPR.
