College of Pharmacy, Research Institute of Pharmaceutical sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea.
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Korea.
Molecules. 2020 Apr 23;25(8):1948. doi: 10.3390/molecules25081948.
A focused PROTAC library was developed to degrade both IGF-1R and Src proteins, which are associated with various cancers. PROTACs with IGF-1R and Src degradation potentials were synthesized by tethering different inhibitor warhead units and the E3 ligase (CRBN) recruiting-pomalidomide with various linkers. The designed PROTACs 12a-b inhibited the proliferation and migration of MCF7 and A549 cancer cells with low micromolar potency (1-5 μM) in various cellular assays.
针对与多种癌症相关的 IGF-1R 和 Src 蛋白，我们开发了一种靶向 PROTAC 文库以进行降解。通过将不同的抑制剂弹头单元和 E3 连接酶（CRBN）招募体（来那度胺）与各种连接子连接，合成了具有 IGF-1R 和 Src 降解潜力的 PROTACs。在所研究的各种细胞实验中，设计的 PROTACs 12a-b 以低微摩尔效力（1-5 μM）抑制 MCF7 和 A549 癌细胞的增殖和迁移。
