NCI Drug Dictionary
The NCI Drug Dictionary contains technical definitions and synonyms for drugs/agents used to treat patients with cancer or conditions related to cancer. Each drug entry includes links to check for clinical trials listed in NCI's List of Cancer Clinical Trials.
- NEDD8 activating enzyme E1 inhibitor TAS4464
An inhibitor of NEDD8 (neural precursor cell expressed, developmentally down-regulated 8) activating enzyme E1 (NAE), with potential antineoplastic activity. Upon administration, TAS4464 selectively binds to and inhibits NAE, which prevents NAE/NEDD8-mediated signaling and prevents the NEDD8 conjugation of cullin-RING ligase complexes (CRLs). This inactivates the CRLs leading to an accumulation of CRL substrate proteins, such as CDT1, p27, p21 and phosphorylated IkappaB, and inactivates nuclear factor-kappaB (NF-kB) as well as downregulates anti-apoptotic proteins. This causes cell cycle dysregulation, induces apoptosis, and inhibits tumor cell proliferation and survival. NAE catalyzes the first step in the NEDD8 conjugation (neddylation) pathway which controls cancer cell growth and survival through activation of CRLs. Check for active clinical trials using this agent. (NCI Thesaurus)
Synonym: NAE inhibitor TAS4464 Code name: TAS4464