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GSK3 has gained a considerable attention of researchers in the late 1970s as an inevitable drug target to treat diabetes. Furthermore, it was found to have a key role in the development of diseases like cancer and neurodegeneration (ND). A broad spectrum of GSK3 inhibitors have been discovered from time to time in order to curb these diseases. Inhibition of GSK3 by insulin boosts the dephosphorylation of glycogen synthase, hence its activation to convert UDP glucose into glycogen. Lack of insulin and insulin-resistance is supposed to be the cause of type 2 diabetes (Diabetes mellitus). Additionally, GSK3 stabilizes the components of beta-catenin complex, hence promotes oncogenesis. Phosphorylation of GSK3 by Akt and some other kinases also favours the carcinogenesis. However, in some cases GSK3 has tumor supressing character. GSK3 has been found to have a prominent role in the formation of amyloid plaques and neurofibrillary tangles (abnormal protein accumulations) which are the main suspects of Alzheimer's disease (AD). GSK3 inhibitors have been reported to have amyloidbeta disaggregation property and have been found to promote the adult hippocampal neurogenesis in vivo as well as in vitro. This manuscript thoroughly reviews the involvement of GSK3 in diabetes, cancer and ND. Furthermore, development of GSK3 inhibitors as antidiabetes, anticancer and antineurodegenerative agents focusing mainly on lead optimization has been discussed.

Triple-negative breast cancer (TNBC) is associated with an increased risk of early recurrence and distant metastasis, as well as the development of therapeutic resistance and poor prognosis. TNBC is characterized by a wide range of genetic, immunophenotypic, morphological, and clinical features. TNBC is coined to describe cancers that lack estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). As a result, hormonal or trastuzumab-based treatments are ineffective in TNBC patients. TNBCs are biologically aggressive, and despite some evidence that they respond to treatment better than other forms of breast cancer, the prognosis remains poor. This is attributed to a shorter disease-free interval in adjuvant and neoadjuvant settings, as well as a more aggressive metastatic course. TNBC has a lot of clinical ramifications. In terms of new treatment methods, TNBC has lagged behind other types of breast cancer. There are not many options for treating this form of breast cancer because it is progressive. Many effective treatments for most breast cancers block the growth-stimulating effects of ER, PR, and/or HER2, leaving TNBC with few choices. Finding new and effective treatment options for TNBC remains a critical clinical need. To develop more effective drugs, new experimental approaches must be tested in patients with TNBC.

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