| Autor: |
Zeng Y; Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu, China.; Blood Diseases Institute, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China., Zhang Y; Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu, China.; Blood Diseases Institute, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China., Cui Z; Blood Diseases Institute, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China., Mao J; Blood Diseases Institute, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China., Xu J; The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu, China., Yao R; Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu, China.; Blood Diseases Institute, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China. |
| Abstrakt: |
Multiple myeloma is a hematological cancer that can be treated but remains incurable. With the advancement of science and technology, more drugs have been developed for myeloma chemotherapy that greatly improve the quality of life of patients. However, relapse remains a serious problem puzzling patients and doctors. Thus, developing more highly active and specific inhibitors is urgent for myeloma-targeted therapy. In this study, we identified the SIRT3 inhibitor 3-TYP (3-(1 H -1,2,3-triazol-4-yl) pyridine) after screening a histone modification compound library, which showed high cytotoxicity and induced DNA damage in myeloma cells. Furthermore, the inhibitory effect of 3-TYP in our xenograft tumor studies also confirmed that compound 3-TYP could inhibit primary myeloma growth by reducing c-Myc protein stability by decreasing c-Myc Ser62 phosphorylation levels. Taken together, the results of our study identified 3-TYP as a novel c-Myc inhibitor, which could be a potential chemotherapeutic agent to target multiple myeloma. |
