Unveiling Novel KRAS G12V Inhibitors: A Comprehensive Study Using Computer-aided Drug Design Approach
Year: 2025
Type: article
Abstract: The KRAS G12V mutation is a formidable oncogenic driver implicated in the pathogenesis of several aggressive cancers, including pancreatic ductal adenocarcinoma, non-small cell lung cancer, and colorectal cancer. Overcoming the historical challenges associated with targeting KRAS mutations, this study harnesses advanced computer-aided drug design (CADD) techniques to unearth novel and potent inhibitors. By leveraging the structural paradigms of clinically validated KRAS inhibitors sotorasib and adagrasib, we systematically screened the PubChem database, yielding 628 promising candidates. Molecular docking simulations pinpointed three standout compounds: CID_138637935, CID_155344829, and CID_165158764, distinguished by their exceptional binding affinities. Subsequent molecular dynamics (MD) simulations offered an in-depth exploration of these compounds, revealing CID_155344829 as the frontrunner, with unparalleled stability, and compact structural integrity. While CID_138637935 and CID_165158764 displayed notable potential, further refinement is warranted. Our findings illuminate the transformative potential of CADD in revolutionizing cancer therapeutics and lay the groundwork for future in vitro and in vivo investigations to validate and optimize these novel KRAS G12V inhibitors.
Authors: Amena Khatun Manica, Benedicta Quainoo, Jonathan Cudjoe, Aminat Motunrayo Adekunle, Cyril Agadagba, Temilade Rukayat Adeniran, Oluwatosin Oluwafunmilola Oluwafemi, Ayomide Daniel Oluwafemi, Abasiodiong Ekanem, Hikmat Opeyemi Sulaiman, Farimah Mohammadi, Emmanuel Parkay Oladokun, Mariam Omowunmi Oguntunji, Roheemah Olamide Oni
Institutions: University of New Haven, Texas Tech University, Kwame Nkrumah University of Science and Technology, University of Lagos, Baylor University, Western Washington University, University of Ilorin, University of Tennessee at Knoxville, Illinois State University, Fountain University, Ladoke Akintola University of Technology
Language: English
Subfield: Computational Theory and Mathematics
Field: Computer Science
Domain: Physical Sciences
Open Access status: diamond
OpenAlex ID: W4409108738