pevonedistat + decitabine + cedazuridine

Pevonedistat + decitabine + cedazuridine is a combination regimen under clinical investigation for higher-risk myelodysplastic syndromes (MDS). Pevonedistat is a small molecule inhibitor of NEDD8-activating enzyme (NAE), disrupting protein degradation and inducing apoptosis in malignant cells. Decitabine is a DNA methyltransferase inhibitor (hypomethylating agent) that can restore normal hematopoiesis and induce cell death of abnormal bone marrow cells. Cedazuridine is a cytidine deaminase inhibitor that increases systemic exposure of decitabine when administered orally. The combination is designed to maximize cytotoxic and hypomethylating effects against dysplastic hematopoietic cells[1][3][5][7].