Recent Progress in Urea-Containing Compounds as Tyrosine Kinase Inhibitors

Cancer remains one of the leading causes of mortality worldwide. Dysregulated cellular signaling pathways play a pivotal role in tumorigenesis, tumor progression, and metastasis. Among these, tyrosine kinases (TKs) constitute a critical class of enzymes that catalyze the phosphorylation of tyrosine residues on target proteins, thereby regulating key cellular processes including growth, differentiation, and survival. TKs have revolutionized cancer therapy by selectively targeting these enzymes, resulting in suppressed tumor growth and improved clinical outcomes for patients. Urea-containing motifs represent one of the most important bioactive functional groups in medicinal chemistry. In particular, unsymmetrical alkyl- and benzylureas are widely employed as key structural components in numerous approved drugs. This structural feature enables versatile modifications that enhance physicochemical properties, including solubility, metabolic stability, and bioavailability. This review explores the current landscape of antineoplastic urea-based tyrosine kinase inhibitors, presenting an exhaustive examination of contemporary urea-containing compounds that inhibit TKs while elucidating their mechanisms of action and molecular targets. In recent years, computational technologies have become indispensable in modern drug discovery. They significantly accelerate the identification of new TKIs and support the repurposing of established pharmaceuticals. Ultimately, the review addresses the prevailing challenges and future opportunities in the advancement of urea-containing tyrosine kinase inhibitors.