Computational Insights into VEGFR1 Inhibitors: Redefining Cancer Treatment through Dual-Targeted Therapy

Worldwide, cancer remains a significant health concern, and great efforts are made continuously to identify new drugs to increase therapeutic efficacy, limit treatment side effects, and overcome drug resistance. In this field, dual/multi-targeted therapy has emerged as a forefront strategy in combating cancers, focusing on disrupting specific molecular pathways essential for tumor growth and progression. In this computational study, we have focused our interest on identifying, among 44 approved anti-cancer drugs, potential VEGF-R1 inhibitors, thereby exhibiting inhibitory effects on angiogenesis. The binding affinity of the tested compounds to the extracellular domain of VEGF-R1 has been performed by using PyRx software and showed that Cladribine, Etoposide, Allopurinol, and Altretamine were the most effective compounds, characterized by promising binding energies ranging between -8.9 to -9.2 kcal/mol. Our computational study clearly showed that Etoposide, Cladribine, Altretamine, and Allopurinol exhibit a great potential affinity to VEGF-R1, suggesting their potential inhibition of VEGF/VEGF-R1 complex that could be of great interest to suppress and block the angiogenic pathway in tumors. Further in silico analyses and experimental investigations are needed to explore the anti-angiogenic effect of these small anti-cancer compounds deeply.