Insight of druggable cannabinoids against estrogen receptor β in breast cancer

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Breast cancer (BC) is a leading global cancer, often driven by estrogen.
• Estrogen receptor beta (ERβ) plays a protective role by suppressing estrogen-induced proliferation.
• Targeting ERβ with small molecules offers a potential therapeutic strategy for BC.

Purpose of the Study:

• To identify and evaluate novel cannabinoid (CB) analogs as potential therapeutic agents for breast cancer.
• To investigate the interaction of CBs with estrogen receptor beta (ERβ) for BC treatment.
• To explore less psychoactive CB derivatives for enhanced drug development.

Main Methods:

• Selection of drug candidates (delta-8-tetrahydrocannabinol and delta-4-isotetrahydrocannabinol) based on ADMET, medicinal chemistry, and physicochemical properties.
• Utilized molecular docking simulations to assess ligand-receptor interactions and binding affinity with ERβ.
• Performed structural modifications on delta-8-tetrahydrocannabinol to create a novel analog, Cannabinoid A.

Main Results:

• Two selected CBs and their analog demonstrated interaction with the active site residues of ERβ.
• Molecular docking simulations provided insights into binding affinity and interaction modes.
• The study identified potential drug candidates for modulating ERβ activity.

Conclusions:

• Cannabinoid analogs, including delta-8-THC and Cannabinoid A, represent a promising new avenue for breast cancer drug discovery.
• Targeting ERβ with these compounds offers a novel therapeutic approach to suppress BC development.
• Further research into these CB derivatives could lead to effective treatments for BC patients.