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Ponatinib: An update on its drug targets, therapeutic potential and safety

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DOI: 10.1016/j.bbcan.2023.188949

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Ponatinib; Chronic myeloid leukemia; Drug targets; Drug combination; Toxicity

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Ponatinib is a multi-target kinase inhibitor used for the treatment of leukemia and other diseases, but its significant cardiovascular toxicity poses a challenge to its clinical use. This article reviews the pharmacokinetics, targets, therapeutic potential, toxicity and production mechanism of ponatinib, and discusses methods to reduce its toxicity.
Leukemia is a malignancy of the hematopoietic system, and as its pathogenesis has become better understood, three generations of tyrosine kinase inhibitors (TKIs) have been developed. Ponatinib is the third-generation breakpoint cluster region (BCR) and Abelson (ABL) TKI, which has been influential in the leukemia therapy for a decade. Moreover, ponatinib is a potent multi-target kinase inhibitor that acts on various kinases, such as KIT, RET, and Src, making it a promising treatment option for triple-negative breast cancer (TNBC), lung cancer, myeloproliferative syndrome, and other diseases. The drug's significant cardiovascular toxicity poses a significant challenge to its clinical use, requiring the development of strategies to minimize its toxicity and side effects. In this article, the pharmacokinetics, targets, therapeutic potential, toxicity and production mechanism of ponatinib will be reviewed. Furthermore, we will discuss methods to reduce the drug's toxicity, providing new avenues for research to improve its safety in clinical use.

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