Inhibitor | Type | Malignancies | Class | EC50/IC50/Dose | Reference |
---|---|---|---|---|---|
Pevonedistat (MLN4924; TAK-924) | Clinical: 33 clinical trials up to phase 3 | Many solid and hematologic malignancies | Adenosine sulfamate | Cell-free thioester formation: 0.0047 μM | Soucy et al., 2009a |
Cell-based neddylation: <0.1 μM | |||||
Cytotoxicity: 0.05–1.03 μM | |||||
In vivo dose: 30–90 mg/kg once daily or twice daily | |||||
TAS4464 (HY-128586) | Clinical: phase 1/2 clinical trial (MM and non-Hodgkin lymphoma) | Many solid and hematologic malignancies | Adenosine aminosulfonamide | Cell-free thioester formation: 0.955 nM | Yoshimura et al., 2019 |
Cytotoxicity ≤10 nM | |||||
In vivo dose: 6.3–100 mg/kg once weekly | |||||
6,6′′-Biapigenin | Experimental | Cell-free and cellular activity in Caco-2 cells | Semisynthetic flavonoid | Cell-free UBC12∼NEDD8 thioester formation: 20 μM | Leung et al., 2011 |
Cell-based UBC12∼NEDD8 thioester formation: 5 μM | |||||
Flavokawain A | Experimental | Prostate, bladder, and urothelial carcinoma | Chalcone flavonoid | Cell-free UBC12∼NEDD8 thioester formation: 5 μM | Zi and Simoneau, 2005; Liu et al., 2013; Li et al., 2015 |
M22 | Experimental | Several cancer cell lines and a mouse model of gastric carcinoma | Piperidin-4-amine | Cytotoxicity: 8.98–26.6 μM | Lu et al., 2016 |
Dose in mice: 60 mg/kg, i.p., once daily | |||||
Piperacillin | Experimental | Cell-free and cellular activity in Caco-2 cells | Semisynthetic β-lactam antibiotic | Cell-free UBC12∼NEDD8 thioester formation:1 μM | Zhong et al., 2014 |
Rhodium (III)-based complex | Experimental | Cell-free and cellular activity in Caco-2 cells | Cyclometallated rhodium(III) complex | Cell-free UBC12∼NEDD8 thioester formation: 1.5 μM | Zhong et al., 2012b |
Cytotoxicity in Caco-2 cells: 0.3 μM | |||||
LZ3 | Experimental | Cell-free and cellular activity in Caco-2, MCF7, and Bel-7402 cells | Sulfonamide derivative | Cell-free UBC12∼NEDD8 thioester formation: 1.06 μM | Zhang et al., 2014 |
Cytotoxicity: 12.3–29.5 μM | |||||
ZM223 | Experimental | Cell-free and cellular activity in colon cancer and osteosarcoma cells | Benzothiazole derivative | Cytotoxicity: 0.1–1.22 μM | Ma et al., 2017 |
Dipeptide-conjugated deoxy-vasicinone | Experimental | Cell-free and cellular activity in Caco-2 cells | Alkaloid derivative | Cell-free UBC12∼NEDD8 thioester formation: 0.8 μM | Zhong et al., 2012a |
Cell-based UBC12∼NEDD8 thioester formation: 6 μM | |||||
Adenosyl-phospho-NEDD8 (APN) | Experimental | Cell-free activity | NEDD8 adenylate | Cell-free NAE-UBC12 transthiolation: 0.05 μM | Brownell et al., 2010 |
pND20 (VI LTFGG) | Experimental | Cell-free activity | Heptameric peptides | Cell-free NAE∼NEDD8 thioester formation: 133 μM | Zhao et al., 2013b |
pND22 (VRLMFGG) | Experimental | Cell-free activity | Heptameric peptides | Cell-free NAE∼NEDD8 thioester formation: 215 μM | Zhao et al., 2013b |
pN1 (VWLSYGG) | Experimental | Cell-free activity | Heptameric peptides | NA | Zhao et al., 2013a |
pN7 (VMLFYGG) | Experimental | Cell-free activity | Heptameric peptides | NA | Zhao et al., 2013a |
pN26 (VLALRGG) | Experimental | Cell-free activity | Heptameric peptides | NA | Zhao et al., 2013a |
NA, not available.