- ISSN: 2210-299X
- E-ISSN: 2210-3007
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oa In-Silico Identification and Characterization of KRAS G12C Inhibitors: Molecular Docking and ADMET Analysis
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Authors:
Palde Omkar Dinkar1
and Sachin Bhosale1
- Source: Current Indian Science, Volume 3, Issue 1, Jan 2025, E2210299X372076
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- 07 Dec 2024
- 20 Mar 2025
- 10 Jun 2025
Abstract
This study aims to identify and evaluate novel KRAS G12C inhibitors using in-silico methods, focusing on molecular docking and ADMET profiling to optimize binding affinity, pharmacokinetics, and safety profiles.
The KRAS G12C mutation is a key driver of oncogenesis in aggressive cancers, including non-small cell lung cancer. Although inhibitors such as sotorasib have been developed, challenges like hepatotoxicity and resistance limit their clinical use.
This study seeks to design and assess potential KRAS G12C inhibitors with superior binding interactions and pharmacokinetic properties compared to existing drugs.
Molecular docking simulations were conducted to evaluate the binding affinities of inhibitors, followed by ADMET profiling to assess pharmacokinetics, drug-likeness, and toxicity.
Novel compounds, such as CID_137278727, demonstrated higher binding affinities (-10.8 kcal/mol) and favourable ADMET profiles compared to sotorasib (-8.1 kcal/mol). Key interactions with residues GLU62, TYR96, and CYS12 were identified, though hepatotoxicity remains a concern.
In-silico approaches have identified promising KRAS G12C inhibitors with enhanced efficacy and pharmacokinetics, highlighting the potential of computational methods in advancing targeted therapies for KRAS-driven cancers.
