报告题目:

诱导致癌蛋白相分离的小分子开发与递送

报告人:

何旺骁

所在单位:

西安交通大学

报告人简介:

略

报告摘要:

Biomolecular condensates are droplet-like membrane-less compartments in cells that can sequester proteins. Modulating these condensates offers a promising way to durably inhibit disease-driving proteins that lack enzymatic activity and thus elude traditional drug targeting. However, many such proteins remain beyond the reach of current condensate-modulating strategies. Here we show an alternative approach: by destabilizing target proteins, we directly induce their liquid–liquid phase separation (LLPS), causing them to form condensates. Using this strategy, we develop a small molecule RQ that forces β-catenin (an oncogenic protein in liver cancer) into cytoplasmic condensates. This sequestration prevents β-catenin from entering the nucleus and activating cancer-promoting genes. In nanoparticle form (albumin-bound Abroquinone), RQ is selectively taken up by β-catenin-driven liver cancer cells and kills them while sparing normal cells. This approach suppresses β-catenin driven tumor growth and overcomes immune evasion, demonstrating a promising paradigm for targeting previously untargetable proteins by inducing their phase separation.