Month/Year of Graduation
5-2025
Degree Name
Bachelor of Science (B.S.)
Department
Chemistry
First Advisor
Joe Yao
Abstract
Receptor tyrosine kinases (RTKs) are vital to cell signaling processes such as growth, survival, and differentiation. Dysregulation through mutation or overexpression often contributes to cancer, making RTKs key therapeutic targets for tyrosine kinase inhibitors (TKIs). However, the low specificity of many TKIs leads to off-target effects. This project uses molecular docking to evaluate the binding affinities and selectivity of FDA-approved TKIs across 18 RTK subtypes. The dockings conducted revealed significant variability in binding affinities, with Sorafenib exhibiting strong specificity for EphB2 (-7.6 kcal/mol) and poor compatibility with EphA7 and ErbB4 (-3.0 kcal/mol). These findings underscore the role of specific molecular interactions, such as hydrogen bonding, in influencing inhibitor selectivity. Overall, the results provide insights into structural determinants of TKI specificity and lay a computational foundation for the rational development of next-generation, highly selective RTK inhibitors. Experimental validation will be essential to confirm these findings.
Recommended Citation
Say, Htoo, "Computationally Assessing the Specificity of Receptor Tyrosine Kinase Inhibitors" (2025). Theses/Capstones/Creative Projects. 370.
https://digitalcommons.unomaha.edu/university_honors_program/370
Included in
Amino Acids, Peptides, and Proteins Commons, Enzymes and Coenzymes Commons, Macromolecular Substances Commons, Organic Chemicals Commons