Structure-based virtual screening discovers novel kidney-type glutaminase inhibitors

Area of Science:

• Biochemistry and Molecular Biology
• Cancer Research
• Drug Discovery

Background:

• Glutaminase (GLS) is crucial for cancer cell bioenergetics and proliferation.
• Targeting glutaminase presents a promising strategy for cancer therapy.
• Novel GLS inhibitors are needed for effective cancer treatment development.

Purpose of the Study:

• To identify novel glutaminase (GLS) inhibitors through structure-based virtual screening.
• To provide insights for the development of new GLS-targeted cancer therapies.
• To evaluate the anticancer potential of identified inhibitors in relevant cancer models.

Main Methods:

• Structure-based virtual screening of potential GLS inhibitors.
• Analysis of pharmacological interactions within the GLS1 binding site.
• Enzymatic assays and cell viability assays using colorectal and triple-negative breast cancer cells.

Main Results:

• Three novel GLS1 inhibitors were identified through virtual screening.
• Selected compounds demonstrated inhibitory effects in enzymatic and cell viability assays.
• Hit compounds showed significant anticancer potential in colorectal and triple-negative breast cancer cell lines.

Conclusions:

• Structure-based virtual screening is an effective method for discovering GLS inhibitors.
• The identified compounds exhibit potential as lead candidates for targeting glutamine metabolism in cancer.
• These findings support the development of new therapeutic strategies against GLS-dependent cancers.