Multifaceted In Silico Screening Strategies Identifies Potent Inhibitors Facilitating Inhibition of ZNF726 Activity...

Area of Science:

• Oncology
• Biochemistry
• Computational Chemistry

Background:

• Zinc finger protein 726 (ZNF726) promotes breast cancer tumorigenesis by elevating cellular cholesterol.
• ZNF726 represents a potential therapeutic target for breast cancer treatment.

Purpose of the Study:

• To identify potent inhibitors of ZNF726 activity using structure-based molecular docking.
• To explore the relationship between ZNF726, cholesterol pathways, and breast cancer progression.

Main Methods:

• Virtual screening of the LOPAC library using molecular docking and MMGBSA scoring.
• Assessing the effect of identified compounds on breast cancer cell proliferation and cholesterol levels.
• Investigating ZNF726's role in regulating cellular cholesterol content.

Main Results:

• Zoledronic acid monohydrate emerged as a top-hit inhibitor of ZNF726, demonstrating significant docking and MMGBSA scores.
• Zoledronic acid monohydrate inhibited breast cancer cell proliferation and reduced cholesterol levels in ZNF726-overexpressing cells.
• Nine phytochemicals with potential ZNF726 inhibitory activity were identified via virtual screening of the IMPPAT library.

Conclusions:

• The cholesterol pathway and oncogenic ZNF726 are interdependent in breast cancer.
• Targeting the cholesterol pathway is a promising strategy to inhibit ZNF726 in breast cancer.
• Zoledronic acid monohydrate and identified phytochemicals warrant further investigation as potential breast cancer therapeutics.