pevonedistat + gemcitabine

Pevonedistat + gemcitabine is a combination of two anticancer agents investigated for use in advanced solid tumors, especially pancreatic and other solid cancers. **Pevonedistat** is a first-in-class small molecule inhibitor of NEDD8-activating enzyme (NAE), which inactivates the neddylation pathway leading to cell cycle arrest and apoptosis. **Gemcitabine** is a nucleoside analog that inhibits DNA synthesis, widely used as a first-line chemotherapy for pancreatic and other cancers. This combination aims to synergistically enhance antitumor effects by combining targeted inhibition of protein degradation (by pevonedistat) with cytotoxic chemotherapy (by gemcitabine)[1][3][2][5]. However, clinical trials indicate that this combination had dose-limiting toxicities, and the combination arm was discontinued due to poor tolerability and adverse events, including febrile neutropenia[1][3].

Other names

pevonedistat plus gemcitabine