Tamibarotene
Tamibarotene
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DOI：
10.1358/dot.2007.43.8.1072615
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发表时间：
2007-08-01
期刊：
影响因子：
1.8
通讯作者：
Kagechika, Hiroyuki
中科院分区：
文献类型：
--
作者：
Miwako, Ishido;Kagechika, Hiroyuki
他米巴罗汀是一种新的合成类维生素A药物，最近在日本批准用于复发或难治性急性早幼粒细胞白血病（APL）。它是视黄酸受体α/β的特异性激动剂。与全反式维甲酸（ATRA）相比，一种用于APL一线治疗的天然类维生素A，他米巴罗汀在化学上更稳定，作为早幼粒细胞白血病细胞分化诱导剂的效力高出数倍。与ATRA相比，其血浆浓度在每日给药期间显著下降，他米巴罗汀维持血浆水平可能是由于对细胞视黄酸结合蛋白的亲和力较低。此外，在临床试验中，不良反应比ATRA轻。在日本进行的临床试验表明，他米巴罗汀对ATRA诱导完全缓解后复发的APL患者有效。最近，更好地了解维甲酸的各种作用机制，激发了人们对其治疗各种疾病的潜在用途的极大兴趣。他米巴罗汀正在临床试验中用于治疗多发性骨髓瘤和克罗恩病。本文综述了他米巴罗汀的作用机制、化学性质、药代动力学及其在APL中的应用以及在各种疾病中的潜在应用。(c)2007年《科学》杂志。All rights reserved.
Tamibarotene is a new synthetic retinoid drug recently approved for relapsed or refractory acute promyelocytic leukemia (APL) in Japan. It is a specific agonist for retinoic acid receptor alpha/beta. Compared to all-trans retinoic acid (ATRA), a natural retinoid indicated for a first-line treatment of APL, tamibarotene is chemically more stable and several times more potent as an inducer of differentiation in promyelocytic leukemia cells. In contrast to ATRA, whose plasma concentration declines considerably during daily administration, tamibarotene sustains plasma level probably due to a lower affinity for cellular retinoic acid binding protein. Furthermore, adverse side effects were milder than those of ATRA in clinical trials. Clinical trials held in Japan showed that tamibarotene had efficacy in APL patients who had relapsed from ATRA-induced complete remission. Recently, better understanding of the various mechanisms of action of retinoids has stimulated great interest in its potential use for treatment of various diseases. Tamibarotene is being investigated for treatment of multiple myeloma and Crohn's disease in clinical trials. This review focuses on tamibarotene's mechanisms of action, chemical properties, pharmacokinetics and its use in APL as well as its potential use in various disorders. (c) 2007 Prous Science. All rights reserved.