Boron-containing anticancer agents: a target-centric review of structure–activity relationships and clinical pipeline

Abstract

Boron, a versatile element historically underexplored in medicinal chemistry, has recently garnered prominence for its unique chemical properties that enable the design of innovative therapeutic compounds. The success of boron-containing drugs such as Bortezomib has spurred interest in developing boron-based compounds targeting a variety of tumor-related proteins. This review provides the first target-centric synthesis of boron-containing anticancer agents, integrating structure-activity relationships, binding mode visualizations, and clinical pipeline status across enzyme and receptor targets. Unlike prior reviews focused on chemistry or individual compound classes, it highlights how boron enables reversible covalent inhibition, prodrug activation, and bioisosteric replacement to overcome resistance and selectivity barriers in oncology. This review highlights the current advancements in boron-containing therapeutics, emphasizing their applications in cancer treatment. The ability to form reversible covalent bonds and interact selectively with biomolecules makes it particularly valuable for enzyme and receptor targeting. Moreover, recent developments have introduced boron-based compounds capable of overcoming drug resistance, enhancing selectivity, and minimizing side effects. This review categorizes boron-containing therapeutics into enzyme-targeting and receptor-targeting categories, discussing their mechanisms of action, preclinical and clinical advancements, and future potential. These advancements establish boron-based chemistry as a powerful tool for overcoming limitations of conventional cancer drugs, paving the way for next-generation oncologic therapies with improved specificity and reduced side effects.