Advances in Isoxazole-Containing Anticancer Drugs: From Synthesis to Clinical Potential

Cancer is one of the most common and deadly diseases worldwide, and the development of new therapeutic strategies to overcome treatment resistance and improve clinical outcomes remains a critical challenge. Heterocyclic compounds have long been recognized as fundamental building blocks in medicinal chemistry. Among them, the isoxazole ring has emerged as a promising pharmacophore in anticancer drug design due to its unique electronic properties and hydrogen-bonding capability. Isoxazole is a five-membered heterocyclic ring containing nitrogen and oxygen atoms at the 1st and 2nd positions, enabling diverse interactions with enzymes and receptors and resulting in a wide range of biological activities. In this review, scientific studies on the development of isoxazole-containing compounds as anticancer agents have been systematically examined from the past to the present. The selected studies were evaluated based on their reported anticancer activity, molecular mechanisms of action, and clinical development status. Isoxazole derivatives have demonstrated significant activity against various cancer types, including breast, lung, colorectal cancers, and leukemia, through mechanisms such as apoptosis induction, cell cycle arrest, kinase inhibition, and suppression of angiogenesis. Moreover, the clinical approval of certain isoxazole-based drugs further supports the translational potential of this scaffold. Overall, the isoxazole core represents a promising and clinically relevant pharmacophore for the development of next-generation targeted anticancer therapies.