非甾体抗炎药是半胱天冬酶抑制剂。
Non-steroidal Anti-inflammatory Drugs Are Caspase Inhibitors.
作者信息
Smith Christina E, Soti Subada, Jones Torey A, Nakagawa Akihisa, Xue Ding, Yin Hang
机构信息
Department of Chemistry & Biochemistry and the BioFrontiers Institute, University of Colorado, Boulder, CO 80309, USA.
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
出版信息
Cell Chem Biol. 2017 Mar 16;24(3):281-292. doi: 10.1016/j.chembiol.2017.02.003. Epub 2017 Feb 23.
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs in the world. While the role of NSAIDs as cyclooxygenase (COX) inhibitors is well established, other targets may contribute to anti-inflammation. Here we report caspases as a new pharmacological target for NSAID family drugs such as ibuprofen, naproxen, and ketorolac at physiologic concentrations both in vitro and in vivo. We characterize caspase activity in both in vitro and in cell culture, and combine computational modeling and biophysical analysis to determine the mechanism of action. We observe that inhibition of caspase catalysis reduces cell death and the generation of pro-inflammatory cytokines. Further, NSAID inhibition of caspases is COX independent, representing a new anti-inflammatory mechanism. This finding expands upon existing NSAID anti-inflammatory behaviors, with implications for patient safety and next-generation drug design.
非甾体抗炎药（NSAIDs）是世界上最常用的药物之一。虽然NSAIDs作为环氧化酶（COX）抑制剂的作用已得到充分证实，但其他靶点可能也有助于抗炎。在此，我们报告半胱天冬酶是布洛芬、萘普生和酮咯酸等NSAIDs家族药物在生理浓度下体外和体内的新药理学靶点。我们在体外和细胞培养中对半胱天冬酶活性进行了表征，并结合计算建模和生物物理分析来确定其作用机制。我们观察到，抑制半胱天冬酶催化可减少细胞死亡和促炎细胞因子的产生。此外，NSAIDs对半胱天冬酶的抑制作用不依赖于COX，代表了一种新的抗炎机制。这一发现扩展了现有的NSAIDs抗炎行为，对患者安全和下一代药物设计具有重要意义。
Zotero 插件