Verra Therapeutics, 127 Asbury Rd., Lansing, NY 14882, USA.
Rumbaugh-Goodwin Institute for Cancer Research, Nova Southeastern University, 3321 College Avenue, CCR 6th Floor, Fort Lauderdale, FL 33328, USA.
Mediators Inflamm. 2017;2017:9673537. doi: 10.1155/2017/9673537. Epub 2017 Nov 2.
Since its discovery, ADAM17, also known as TNF converting enzyme or TACE, is now known to process over 80 different substrates. Many of these substrates are mediators of cancer and inflammation. The field of ADAM metalloproteinases is at a crossroad with many of the new potential therapeutic agents for ADAM17 advancing into the clinic. Researchers have now developed potential drugs for ADAM17 that are selective and do not have the side effects which were seen in earlier chemical entities that targeted this enzyme. ADAM17 inhibitors have broad therapeutic potential, with properties ranging from tumor immunosurveillance and overcoming drug and radiation resistance in cancer, as treatments for cardiac hypertrophy and inflammatory conditions such as inflammatory bowel disease and rheumatoid arthritis. This review focuses on substrates and inhibitors identified more recently for ADAM17 and their role in cancer and inflammation.
自发现以来,ADAM17(也称为 TNF 转化酶或 TACE)现已被证实可加工超过 80 种不同的底物。其中许多底物是癌症和炎症的介质。ADAM 金属蛋白酶领域正处于十字路口,许多针对 ADAM17 的新型潜在治疗药物正在进入临床。研究人员现已开发出针对 ADAM17 的选择性潜在药物,这些药物没有早期针对该酶的化学实体所观察到的副作用。ADAM17 抑制剂具有广泛的治疗潜力,具有从肿瘤免疫监视到克服癌症中的药物和辐射耐药性、治疗心脏肥大以及炎症性疾病(如炎症性肠病和类风湿性关节炎)等特性。本文重点介绍了最近为 ADAM17 鉴定的底物和抑制剂及其在癌症和炎症中的作用。