Song, Jian; Cui, Xin-Xin; Wu, Bo-Wen; Li, Dong; Wang, Sheng-Hui; Shi, Lei; Zhu, Ting; Zhang, Yan-Bing; Zhang, Sai-Yang published the artcile< Discovery of 1,2,4-triazine-based derivatives as novel neddylation inhibitors and anticancer activity studies against gastric cancer MGC-803 cells>, Computed Properties of 4956-05-2, the main research area is neddylation triazine UBC12 NEDD8 conjugation antiproliferative anticancer activity; 1,2,4-Triazine; MGC-803; Neddylation; UBC12-NEDD8 conjugation.
Neddylation modification is often over-expressed in a variety of human tumor cells. Therefore, targeting neddylation pathway may represent a potential approach to the treatment of human tumors. Herein, we describe the discovery of a hit scaffold from our inhouse library and further structure-based optimizations. In this work, compound V11 could block the neddylation and inhibit the activity of NAE (with an EC50 value of 3.56μM), and a dose-dependent reduction of the Ubc12-NEDD8 conjugations was also observed Mol. docking results suggest compound V11 could bind tightly to NAE via hydrogen bonds and hydrophobic interactions. Compound V11 showed the best antiproliferative ability with an IC50 value of 8.22μM against gastric cancer MGC-803 cells. Further anticancer activity studies suggested that compound V11 inhibited MGC-803 cell growth, caused a cell cycle arrestment at G2/M phase and induced apoptosis via extrinsic and intrinsic apoptosis pathways. All the findings suggest that 1,2,4-triazine scaffold might provide a novel scaffold for the further development of neddylation inhibitors and compound V11 might be a potential neddylation inhibitor with anticancer activity.
Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 4956-05-2 belongs to class pyrimidines, and the molecular formula is C3H2BrN3O2, Computed Properties of 4956-05-2.
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia