State Key Laboratory of Microbial Metabolism, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
State Key Laboratory of Microbial Metabolism, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
Eur J Med Chem. 2016 Oct 21;122:178-184. doi: 10.1016/j.ejmech.2016.06.018. Epub 2016 Jun 14.
The small ubiquitin-related modifier (SUMO)-specific proteases (SENPs) catalyze the deconjugation of SUMO from their substrate proteins. SENP1 which is the most studied isoform is closely related to many cancers such as prostate cancer and colon cancer, thus representing a potential therapeutic target for cancer treatment. In the present study, we identified eleven SENP1 inhibitors representing a variety of scaffolds through in silico screening. Based on these scaffolds, a series of new compounds were designed and synthesized in order to improve their SENP1 inhibitory potency. As a result, compounds with IC50 as low as 3.5 μM (compound 13m) were obtained and a preliminary structure-activity relationship was discussed.
小泛素相关修饰物（SUMO）特异性蛋白酶（SENP）催化 SUMO 从其底物蛋白上的去共轭。SENP1 是研究最为广泛的同工酶，与许多癌症密切相关，如前列腺癌和结肠癌，因此代表了癌症治疗的一个潜在治疗靶点。在本研究中，我们通过计算机筛选鉴定了十一种代表多种支架的 SENP1 抑制剂。基于这些支架，设计并合成了一系列新的化合物，以提高它们对 SENP1 的抑制能力。结果，获得了 IC50 低至 3.5μM 的化合物（化合物 13m），并讨论了初步的构效关系。
