用于蛋白质 ADP 核糖基化的 PARP1 选择性抑制剂的发现。
Discovery of PARP1-Sparing Inhibitors for Protein ADP-Ribosylation.
作者信息
Stephens Elisa N, Chen Liang-Chieh, Ansari Arshad J, Shen Kaiyu, Zhang Lei, Guillen Steven G, Wang Clay C C, Zhang Yong
机构信息
Department of Pharmacology and Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, California 90089, United States.
Department of Chemistry, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, California 90089, United States.
出版信息
ACS Med Chem Lett. 2024 Oct 30;15(11):1940-1946. doi: 10.1021/acsmedchemlett.4c00395. eCollection 2024 Nov 14.
Poly-ADP-ribose polymerases (PARPs) that catalyze cellular ADP-ribosylation play important roles in human health. PARP inhibitors have found success in the clinic for cancer treatment. However, isoform-specific inhibitors are needed for improved safety. Here, we report the unexpected discovery of nicotinamide mimics that block non-PARP1-catalyzed ADP-ribosylation at micromolar concentrations. These PARP1-sparing PARP inhibitors represent first-in-class probes for ADP-ribosylation, shedding light on the selective inhibition of PARPs.
催化细胞ADP核糖基化的聚ADP核糖聚合酶（PARP）在人类健康中发挥着重要作用。PARP抑制剂已在癌症治疗临床中取得成功。然而，为了提高安全性，需要亚型特异性抑制剂。在此，我们报告了意外发现的烟酰胺类似物，它们在微摩尔浓度下可阻断非PARP1催化的ADP核糖基化。这些保留PARP1的PARP抑制剂代表了用于ADP核糖基化的一流探针，为PARP的选择性抑制提供了线索。
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