Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, USA.
Departments of Medicine and Pathology, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.
Int J Mol Sci. 2020 Sep 8;21(18):6556. doi: 10.3390/ijms21186556.
Abl1 kinase has important biological roles. The Bcr-Abl1 fusion protein creates undesired kinase activity and is pathogenic in 95% of chronic myeloid leukemia (CML) and 30% of acute lymphoblastic leukemia (ALL) patients. Targeted therapies to these diseases are tyrosine kinase inhibitors. The extent of a tyrosine kinase inhibitor's targets determines the degree of biologic effects of the agent that may influence the well-being of the patient. This fact is especially true with tyrosine kinase inhibitor effects on the cardiovascular system. Thirty-one percent of ponatinib-treated patients, the tyrosine kinase inhibitor with the broadest inhibitory spectrum, have thrombosis associated with its use. Recent experimental investigations have indicated the mechanisms of ponatinib-associated thrombosis. Further, an antidote to ponatinib is in development by re-purposing an FDA-approved medication.
Abl1 激酶具有重要的生物学作用。Bcr-Abl1 融合蛋白产生了不必要的激酶活性，是 95%的慢性髓性白血病（CML）和 30%的急性淋巴细胞白血病（ALL）患者的致病因素。针对这些疾病的靶向治疗方法是酪氨酸激酶抑制剂。酪氨酸激酶抑制剂的靶点范围决定了药物的生物学效应程度，这可能会影响患者的健康状况。对于酪氨酸激酶抑制剂对心血管系统的影响，这一事实尤其如此。在接受治疗的患者中，有 31%的患者因使用酪氨酸激酶抑制剂波那替尼而出现血栓形成，该药具有最广泛的抑制谱。最近的实验研究表明了与波那替尼相关的血栓形成的机制。此外，正在通过重新利用一种 FDA 批准的药物来开发一种针对波那替尼的解毒剂。
