Chhina Mantej K, Nargues Weir, Grant Geraldine M, Nathan Steven D
Molecular & Microbiology Department, George Mason University, 10900 University Blvd, 109 Manassas, VA 20110 USA.
Future Cardiol. 2010 Jan;6(1):19-35. doi: 10.2217/fca.09.54.
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.
甲磺酸伊马替尼是一种小分子抑制剂，它能选择性抑制血小板衍生生长因子（PDGF）受体激酶以及cKIT和Abl激酶等靶点。多项研究表明，PDGF途径与肺动脉高压（PAH）的发病机制有关。甲磺酸伊马替尼的抑制作用在PAH的人类病例报告和实验模型中已显示出疗效。甲磺酸伊马替尼治疗PAH的II期试验结果未达到主要终点，但在几个次要终点和亚组分析中显示出改善。正如本研究以及一些病例报告所表明的那样，伊马替尼可能对一部分病情较重的患者有效。然而，这仍有待通过一项已经在进行的III期研究进一步验证。总之，甲磺酸伊马替尼似乎有望成为PAH治疗中的辅助药物，特别是因为它针对的是一个以前未被靶向的途径。
