Bioinformatic Discovery of Novel FGFR-۱ Inhibitors from Natural Products: A Promising Approach for Lung Cancer Treatment

Lung cancer is a prevailing and substantially type of cancer that is attributed to a significantnumber of cancer-related fatalities due to its highly metastatic nature. While current therapies suggestsome benefits, they often face limitations such as toxicity and drug resistance, highlighting the urgentneed for novel and more effective treatment options. Natural products, with their rich phytochemicalprofiles and reduced toxicity, have emerged as promising candidates for therapeutic development. Thisstudy employed a bioinformatic approach to identify bioactive phytochemicals with potential efficacyin targeting fibroblast growth factor receptor ۱ (FGFR-۱), a key regulator of the extracellular signalregulatedkinase (ERK) pathway in cancer progression. A comprehensive analysis of over ۸,۰۰۰phytocompounds from the ZINC۱۵ database was conducted against FGFR-۱ as the target protein,obtained from the Protein Data Bank (PDB). Docking simulations were performed using SchrodingerMaestro ۱۱.۵ to evaluate the glide emodel and docking score of these phytochemicals with FGFR-۱.The top-performing compounds were further assessed using Pyrx virtual screening to assess theirbinding affinity and calculate root mean square deviation (RMSD). To assess their pharmacokineticproperties, the compounds were evaluated using the Admetlab۲ database. Among the screenedphytochemicals, ZINC۵۰۷۵۲۳۸ with Glide emodel= -۶۸.۵۲, docking score = -۶.۹۳۳ binding affinity= -۸ and RMSD=۰ exhibited significantly higher binding interaction to FGFR-۱ compared to thecommercially available FGFR-۱ inhibitor pemigatinib, while also possessing favorablepharmacokinetic properties. This finding presents a promising lead for the development of novel naturalproduct-derived FGFR-۱ inhibitors. Further studies are warranted to validate the efficacy and safety ofZINC۵۰۷۵۲۳۸ in preclinical models and clinical trials. In conclusion, this study demonstrates thepotential of utilizing a bioinformatic approach to identify novel bioactive phytochemicals withpromising therapeutic applications in lung cancer. The discovery of ZINC۵۰۷۵۲۳۸ as a FGFR-۱inhibitor emphasizes the value of natural products as therapeutic agents.

کلیدواژه ها:

FGFR-۱ ، lung cancer ، Drug design ، Anti-cancer agents ، Phytochemicals