Targeting the Ubiquitin-conjugating Enzyme for Oral Squamous Cell Carcinoma Therapy: Discovering Natural Inhibitors

Oral Squamous Cell Carcinoma (OSCC) is a multiple-phase carcinogenic disease that concurrently involves malignant lesions, invasion, and metastasis. It has been reported that Ubiquitin-conjugating enzymes play a significant role in the progression of OSCC and other fatal cancers through the process of ubiquitination. Among them, UBE2D1 represents a promising target for therapeutic intervention. Strategies aimed at inhibiting UBE2D1 could restore the function of tumor suppressors, such as p53, and potentially enhance the effectiveness of existing cancer therapies.

This study aims to discover the potential natural inhibitors of UBE2D1 from an extensive chemical library through computational techniques.

This study utilized in silico methods, such as virtual screening, molecular docking, analysis of pharmacokinetic parameters, and molecular dynamics simulation, to discover the most effective inhibitors for the ubiquitin-conjugating enzyme.

Based on binding affinity, the top six compounds, ZINC15113777, ZINC225461658, ZINC107430641, ZINC259440, ZINC4025306, and ZINC107283931, were found to be the best for the selected target. Also, molecular dynamic simulation results showed that all these compounds form stable complexes with UBE2D1.

Based on our analysis of the results, we have determined that natural products, specifically ZINC15113777, ZINC4025306, and ZINC107283931, have the ability to inhibit UBE2D1 efficiently and could be utilized as potential drugs for the treatment of OSCC and other cancers. Such approaches may help to reinstate normal apoptotic pathways and improve overall treatment outcomes in patients with cancers characterized by UBE2D1 dysregulation. Additionally, conducting in-vitro/vivo studies on these molecules could be a prospective avenue in the realm of pharmaceutical research.