What is ponatinib? Full explanation of pharmacological mechanisms, indications and clinical use

Ponatinib (Ponatinib) is an oral third-generation tyrosine kinase inhibitor (TKI), mainly used to treat chronic myeloid leukemia (CML) and chronic myelogenous leukemia (CML) that are resistant or intolerant to other TKI Philadelphia Chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) patients. As a multi-target inhibitor, ponatinib specifically targets BCR-ABL kinase and its T315I mutation. It has a significant inhibitory effect and is an important treatment option for patients with drug-resistant mutations that cannot be covered by traditional first- and second-generation TKIs.

In terms of pharmacological mechanism, ponatinib selectively binds to the ATP binding site of BCR-ABL kinase and inhibits its enzymatic activity, thereby blocking the proliferation signal of leukemia cells. Unlike early TKI , ponatinib can effectively inhibit multiple drug-resistant mutants BCR-ABL including T315I , thereby overcoming the problem of traditional drug resistance. In addition, ponatinib can also inhibit various tyrosine kinases such as VEGFR, FGFR and PDGFR , and has a certain impact on the tumor microenvironment and angiogenesis, which also provides a theoretical basis for its application in some leukemias and drug-resistant tumors.

In terms of clinical indications, ponatinib has been approved by FDA and domestic drug regulatory authorities. It is mainly used to treat chronic phase, accelerated phase and blast crisis CML Patients, especially those who are resistant to imatinib (Imatinib), dasatinib (Dasatinib) or nilotinib (Nilotinib), and also suitable for T315I Mutation-positive Ph+ ALL patients. Clinical data show that ponatinib can significantly improve the molecular response rate and hematological response rate in drug-resistant patients, help achieve disease control, and provide a feasible option for subsequent transplantation or long-term management.

In actual clinical use, the dosage and course of treatment of ponatinib need to be adjusted individually based on the patient's disease course, drug resistance, vascular risk and other factors. Common adverse reactions include thrombotic events, rash, diarrhea, thrombocytopenia, and hypertension. Therefore, cardiovascular status, blood routine, and liver and kidney function need to be strictly monitored during medication. Through scientific dose management and safety monitoring, ponatinib can achieve better efficacy in patients with drug-resistant leukemia while taking into account safety, providing an important clinical treatment option to overcome multiple drug-resistant mutations.

Keyword tag:

Ponatinib, Ponatinib, pharmacological mechanism, indications, clinical use, CML, ALL, T315I mutation, drug resistance, adverse reaction management, cardiovascular monitoring

Reference:https://en.wikipedia.org/wiki/Ponatinib