The Selective SIRT3 Inhibitor 3-TYP Represses Primary Myeloma Growth by Reducing c-Myc Stability.
Yindi ZengYaxin ZhangZeyu CuiJiwei MaoJinge XuRuosi YaoPublished in: Chemical research in toxicology (2024)
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.
Keyphrases
- multiple myeloma
- newly diagnosed
- end stage renal disease
- dna damage
- chronic kidney disease
- ejection fraction
- oxidative stress
- peritoneal dialysis
- public health
- dna methylation
- prognostic factors
- gene expression
- induced apoptosis
- patient reported outcomes
- climate change
- ischemia reperfusion injury
- small molecule
- cell proliferation
- papillary thyroid
- free survival
- protein protein