CSN5i-3

CSN5i-3 is a potent, selective, and orally bioavailable **inhibitor of the proteolytic subunit CSN5 (JAB1)** of the COP9 signalosome (CSN) complex. The CSN complex is essential for the regulation of cullin-RING E3 ubiquitin ligases (CRLs), which mediate protein ubiquitination and degradation within the ubiquitin–proteasome system (UPS). **CSN5i-3 traps CRLs in a neddylated (active) state**, causing auto-inactivation and degradation of their substrate recognition modules, leading to impaired cell cycle progression and increased apoptosis in cancer cells. It demonstrates antitumor activity across various preclinical cancer models, including prostate cancer, breast cancer, anaplastic large cell lymphoma, and ovarian cancer. CSN5i-3 is being researched as an anti-cancer agent and for its unique effects on immune and inflammatory signaling pathways (e.g., induction of type-I interferon response, modulation of NF-κB pathways)[1][3][4][5][6].