Evaluation of imatinib mesylate in the treatment of pulmonary arterial hypertension
Evaluation of imatinib mesylate in the treatment of pulmonary arterial hypertension
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DOI：
10.2217/fca.09.54
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发表时间：
2010-01-01
影响因子：
1.7
通讯作者：
Nathan, Steven D.
中科院分区：
文献类型：
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作者：
Chhina, Mantej K.;Nargues, Weir;Nathan, Steven D.
甲磺酸伊马替尼是一种小分子抑制剂，可选择性抑制PDGF受体激酶、cKIT和Abl激酶等靶点。各种研究表明PDGF通路与肺动脉高压（PAH）的发病机制有关。甲磺酸伊马替尼的抑制作用在人类病例报告和实验模型中显示出有效性。甲磺酸伊马替尼治疗PAH的II期试验结果没有达到主要终点，但在几个次要终点和亚组分析中显示出改善。正如这项研究以及一些病例报告所表明的，伊马替尼可能对一些疾病更严重的患者有效。然而，这仍然需要通过III期研究进一步验证，该研究已经在进行中。总之，甲磺酸伊马替尼似乎有望作为PAH治疗的辅助药物，特别是因为它是针对以前没有靶向的途径。
Imatinib mesylate is a small molecule inhibitor that selectively inhibits the PDGF receptor kinase as well the cKIT and Abl kinases, among other targets. Various studies have implicated the PDGF pathway in the pathogenesis of pulmonary arterial hypertension (PAH). Inhibition with imatinib mesylate has shown efficacy in human case reports and experimental models of PAH. Results from a Phase II trial of imatinib mesylate in PAH did not meet the primary end point but showed improvement in several secondary end points and in a subgroup analysis. As suggested by this study as well as a few case reports, imatinib may be effective in a subset of patients with more severe disease. However, this remains to be further validated through a Phase III study, which is already underway. In conclusion, it appears that imatinib mesylate may hold promise as an adjunct drug in PAH therapy, especially since it is directed at a pathway not previously targeted.