Zindler Melanie, Pinchuk Boris, Renn Christian, Horbert Rebecca, Döbber Alexander, Peifer Christian
Christian Albrechts University of Kiel, Institute of Pharmacy, Gutenbergstr. 76, 24118 Kiel (Germany).
ChemMedChem. 2015 Aug;10(8):1335-8. doi: 10.1002/cmdc.201500163. Epub 2015 Jun 15.
Imatinib is the first protein kinase inhibitor approved for clinical use and is a seminal drug for the concept of targeted therapy. Herein we report on the design, synthesis, photokinetic properties, and in vitro enzymatic evaluation of a photoactivatable caged prodrug of imatinib. This approach allows spatial and temporal control over the activation of imatinib triggered by ultraviolet light. The successful application of the photoactivation concept to this significant kinase inhibitor provides further evidence for the caging technique as a feasible approach in the kinase field. The presented photoactivatable imatinib prodrug will be highly useful as a pharmacological tool to study the impact of imatinib toward biological systems in greater detail.
伊马替尼是首个被批准用于临床的蛋白激酶抑制剂，是靶向治疗概念的开创性药物。在此，我们报告伊马替尼光活化笼形前药的设计、合成、光动力学性质及体外酶活性评估。这种方法能够对紫外线触发的伊马替尼活化进行空间和时间控制。光活化概念在这种重要激酶抑制剂上的成功应用，为笼形技术作为激酶领域一种可行方法提供了进一步证据。所展示的光活化伊马替尼前药作为一种药理学工具，将非常有助于更详细地研究伊马替尼对生物系统的影响。
