Molecular docking based screening analysis of GSK3B

Area of Science:

• Biochemistry
• Oncology
• Pharmacology

Background:

• Glycogen synthase kinase 3 beta (GSK3B) is implicated in non-communicable diseases, including cancer, Alzheimer's, and type 2 diabetes.
• While GSK3B inhibition shows therapeutic benefits in Alzheimer's disease, its role in various cancers remains unclear.
• Dysfunctional GSK3B expression has prognostic significance in major causes of mortality.

Purpose of the Study:

• To investigate the contribution and prognostic significance of GSK3B in ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC).
• To identify and computationally optimize novel GSK3B inhibitors for breast cancer therapy.

Main Methods:

• Utilized the Oncomine platform to analyze GSK3B expression in breast cancer subtypes.
• Performed high-throughput screening and molecular docking to identify potential inhibitors.
• Conducted computational hit optimization and ADME profiling for lead compounds.

Main Results:

• GSK3B's contribution and prognostic significance were evaluated in DCIS and IDC.
• Identified BT-000775 as a potent GSK3B inhibitor through molecular docking and screening.
• BT-000775 demonstrated high selectivity, superior binding affinity, and favorable ADME profiles.

Conclusions:

• GSK3B plays a significant role in breast cancer subtypes (DCIS and IDC).
• BT-000775 is a promising, highly selective GSK3B inhibitor with potential therapeutic applications in breast cancer.
• Further research into BT-000775 is warranted for its development as a breast cancer therapeutic agent.