Discovery of Therapeutic Lead Molecule Against β-Tubulin Using Computational Approach

Area of Science:

• Pharmacology
• Computational Chemistry
• Oncology

Background:

• Paclitaxel resistance in blood cancers is a significant clinical challenge, often driven by mutations like A185T and A248V in the β-tubulin target.
• Developing novel therapeutic strategies is crucial to overcome this resistance and improve patient outcomes.

Purpose of the Study:

• To identify potential drug candidates capable of overcoming paclitaxel resistance by targeting β-tubulin.
• To discover novel inhibitors for paclitaxel-resistant cancer types through virtual screening.

Main Methods:

• Virtual screening of compounds from the NPACT database against the β-tubulin target.
• Filtering compounds based on pharmacokinetic properties, toxicity, and binding energy.
• Hierarchical clustering to analyze compound features.

Main Results:

• Identified 5 active compounds from an initial list of 1574 bioactive compounds.
• Glaucarubol, derived from Ailanthus excelsa, emerged as a promising lead molecule.
• This is the first reported observation of glaucarubol's inhibitory action against β-tubulin.

Conclusions:

• Glaucarubol demonstrates potential as a therapeutic agent for paclitaxel-resistant cancers.
• Further experimental validation is warranted to confirm glaucarubol's efficacy and mechanism of action.
• The study highlights the utility of virtual screening in discovering novel anti-cancer compounds.