Affiliation:
1. Computational Biology and Molecular Simulations Laboratory Department of Biophysics School of Medicine Bahçeşehir University 34734 Istanbul Turkey
2. Lab for Innovative Drugs (Lab4IND) Computational Drug Design Center (HİTMER) Bahçeşehir University 34734 İstanbul Türkiye
3. Molecular Therapy Lab (MTL) Department of Pharmaceutical Chemistry School of Pharmacy Bahçeşehir University 34353 Istanbul Türkiye
Abstract
AbstractThe RAS‐MAPK signaling pathway, crucial for cell proliferation and differentiation, involves key proteins KRAS and SOS1. Mutations in the KRAS and SOS1 genes are implicated in various cancer types, including pancreatic, lung, and juvenile myelomonocytic leukemia. There is considerable interest in identifying inhibitors targeting KRAS and SOS1 to explore potential therapeutic strategies for cancer treatment. In this study, advanced in silico techniques were employed to screen small molecule libraries at this interface, leading to the identification of promising lead compounds as potential SOS1 inhibitors. Comparative analysis of the average binding free energies of these predicted potent compounds with known SOS1 small molecule inhibitors revealed that the identified compounds display similar or even superior predicted binding affinities compared to the known inhibitors. These findings offer valuable insights into the potential of these compounds as candidates for further development as effective anti‐cancer agents.