Zhang Zhihong, Meier Kathryn E
Department of Pharmaceutical Sciences, P.O. Box 646534, Washington State University, Pullman, WA 99164-6534, USA.
Mol Pharmacol. 2006 May;69(5):1510-2. doi: 10.1124/mol.106.023721. Epub 2006 Feb 23.
An article presented in this issue of Molecular Pharmacology (p. 1527) provides an intriguing example of how tyrosine kinase inhibitors can be put to many uses. In this article, the action of dasatinib (BMS-354825) is contrasted with that of imatinib, a kinase inhibitor that is currently being used to treat chronic myelogenous leukemia and other disorders. Both pharmacologic inhibitors target several tyrosine kinases, including Bcr-Abl and the platelet-derived growth factor receptor (PDGFR). Up to this point, the PDGFR has not been a primary therapeutic target for this class of agents. The work of Chen and colleagues shows that dasatinib is a particularly potent inhibitor of PDGFR and that the compound also targets Src kinase. The authors suggest that this combination of activities could be useful in the treatment of vascular obstructive diseases. Although a lack of absolute specificity has typically been regarded as a pharmacologic drawback, this study exemplifies how drugs with multiple molecular targets can potentially provide a very beneficial spectrum of therapeutic activities in multiple disease states.
本期《分子药理学》（第1527页）发表的一篇文章提供了一个有趣的例子，说明了酪氨酸激酶抑制剂如何能有多种用途。在这篇文章中，达沙替尼（BMS - 354825）的作用与伊马替尼形成对比，伊马替尼是一种目前用于治疗慢性粒细胞白血病和其他疾病的激酶抑制剂。这两种药物抑制剂都靶向多种酪氨酸激酶，包括Bcr - Abl和血小板衍生生长因子受体（PDGFR）。到目前为止，PDGFR尚未成为这类药物的主要治疗靶点。陈及其同事的研究表明，达沙替尼是一种特别有效的PDGFR抑制剂，并且该化合物还靶向Src激酶。作者认为，这种活性组合可能对治疗血管阻塞性疾病有用。虽然缺乏绝对特异性通常被视为药物的一个缺点，但这项研究例证了具有多个分子靶点的药物如何有可能在多种疾病状态下提供非常有益的治疗活性谱。
