Narayanan V, Gutman J A, Pollyea D A, Jimeno A
Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
Drugs Today (Barc). 2013 Jul;49(7):447-56. doi: 10.1358/dot.2013.49.6.1980495.
Omacetaxine mepesuccinate is a protein synthesis inhibitor that causes apoptosis of chronic myeloid leukemia cells without binding to the BCR-ABL tyrosine kinase that is implicated in the pathogenesis of this disease. It has been approved for the treatment of chronic myeloid leukemia in patients with resistance to two or more tyrosine kinase inhibitors and is emerging as an important agent in countering the highly resistant T315I mutation. This review will focus on the preclinical pharmacology, pharmacokinetics and clinical utility of omacetaxine mepesuccinate in the current milieu of tyrosine kinase inhibitor-dominant therapy of chronic myeloid leukemia.
马普替林奥马西他辛是一种蛋白质合成抑制剂,可导致慢性粒细胞白血病细胞凋亡,且不与该疾病发病机制中涉及的BCR-ABL酪氨酸激酶结合。它已被批准用于治疗对两种或更多酪氨酸激酶抑制剂耐药的慢性粒细胞白血病患者,并正成为对抗高度耐药T315I突变的重要药物。本综述将聚焦于马普替林奥马西他辛在当前酪氨酸激酶抑制剂主导的慢性粒细胞白血病治疗环境中的临床前药理学、药代动力学及临床应用。