Searching for potential mTOR inhibitors: Ligand-based drug design, docking and molecular dynamics studies of...

Area of Science:

• Biochemistry
• Pharmacology
• Molecular Biology

Background:

• The PI3K/Akt/mTOR pathway regulates cell cycle and is implicated in various diseases.
• Dysregulation of this pathway is a key factor in disease pathogenesis.
• Current mTOR inhibitors like rapamycin have limitations, necessitating new therapeutic strategies.

Purpose of the Study:

• To discover novel non-ATP competitive inhibitors of the mechanistic target of rapamycin (mTOR) complex.
• To identify potential drug candidates with improved properties compared to existing inhibitors.
• To explore advanced drug design strategies for targeting the mTOR pathway.

Main Methods:

• Utilized ligand-based drug design, including pharmacophore searching and analysis.
• Performed molecular docking and ADMETox property filtering for candidate selection.
• Employed molecular dynamics simulations to evaluate inhibitor behavior.

Main Results:

• Identified eight novel molecular entities with potential as mTOR inhibitors.
• These candidates demonstrated promising computational properties.
• The proposed inhibitors may offer an alternative to rapamycin with potentially fewer side effects.

Conclusions:

• Successfully identified eight novel potential non-ATP competitive mTOR inhibitors.
• The developed molecules exhibit favorable predicted properties for therapeutic development.
• This study provides a foundation for developing new treatments targeting the mTOR pathway.