Identification of polypharmacological anticancerous molecules against Aurora kinase family of proteins

Area of Science:

• Biochemistry
• Molecular Biology
• Cancer Research

Background:

• Human Aurora Kinase (AURK) proteins are crucial for cell cycle regulation.
• Aberrant AURK expression is linked to chromosomal instability and cancer development.
• Existing AURK inhibitors face challenges with toxicity and safety in clinical trials.

Purpose of the Study:

• To identify novel molecules targeting all three AURK proteins using a computational polypharmacological strategy.
• To evaluate the binding stability of identified molecules within the ATP binding pocket.
• To explore potential new therapeutic agents for cancer treatment.

Main Methods:

• Computational polypharmacology approach.
• Identification of novel small molecules targeting AURK family.
• Molecular dynamics simulations to assess binding stability at the ATP pocket.

Main Results:

• Four novel molecules were identified as potential inhibitors of all three AURK proteins.
• Molecular dynamics simulations demonstrated favorable binding stabilities for these molecules.
• The identified compounds show promise for targeting AURKs in cancer therapeutics.

Conclusions:

• The study successfully identified novel polypharmacological inhibitors of AURKs using computational methods.
• These molecules exhibit promising binding stability, suggesting potential for cancer therapeutics.
• The findings offer a new avenue for developing safer and more effective AURK-targeted cancer treatments.