In-silico investigation of RPS6KB1 associated cancer inhibitor: a drug repurposing study

Area of Science:

• Biochemistry
• Molecular Biology
• Pharmacology

Background:

• Ribosomal protein S6 kinase beta-1 (RPS6KB1), or p70S6 kinase, is implicated in diabetes, obesity, and cancer.
• RPS6KB1 activity is regulated by phosphorylation, notably at Threonine 389 by mTORC1 and Threonine 229 by PDK1.
• The full spectrum of RPS6KB1-related biological phenomena requires further investigation.

Purpose of the Study:

• To identify novel inhibitors of RPS6KB1 using computational methods.
• To assess the binding affinity, stability, and drug-likeness of potential RPS6KB1 inhibitors.
• To lay the groundwork for developing new cancer therapeutics targeting RPS6KB1.

Main Methods:

• Virtual screening of the ZINC chemical library.
• Molecular docking simulations to predict binding interactions.
• Molecular dynamics (MD) simulations and MMGBSA calculations for affinity and stability assessment.
• Evaluation of drug-likeness properties of identified compounds.

Main Results:

• Identification of several potential RPS6KB1 inhibitors from the ZINC database.
• Selected compounds demonstrated favorable binding affinity and stability through MD and MMGBSA analyses.
• Comparative analysis confirmed the potential of identified molecules against native RPS6KB1 and co-crystal ligands.

Conclusions:

• The study successfully identified promising small molecules targeting RPS6KB1.
• These compounds warrant further investigation in preclinical (in vitro) and clinical (in vivo) studies.
• The findings contribute to the development of novel therapeutic strategies for cancer treatment.