DI-1859
目录号 : GC65576DI-1859 是一种有效的、选择性的、共价的 DCN1 抑制剂。DI-1859 在低纳摩尔浓度下抑制细胞中 cullin 3 的 neddylation。DI-1859 诱导小鼠肝脏中 NRF2 蛋白(一种 CRL3 底物)的强烈增加,并有效保护小鼠免受对乙酰氨基酚诱导的肝损伤。
Cas No.:2247061-09-0
Sample solution is provided at 25 µL, 10mM.
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DI-1859 is a potent, selective and covalent inhibitor of DCN1. DI-1859 inhibits neddylation of cullin 3 in cells at low nanomolar concentrations. DI-1859 induces a robust increase of NRF2 protein, a CRL3 substrate, in mouse liver and effectively protects mice from acetaminophen-induced liver damage[1].
[1]. Zhou H, et al. Selective inhibition of cullin 3 neddylation through covalent targeting DCN1 protects mice from acetaminophen-induced liver toxicity. Nat Commun. 2021;12(1):2621.
Cas No. | 2247061-09-0 | SDF | Download SDF |
分子式 | C30H45N5O3S | 分子量 | 555.78 |
溶解度 | 储存条件 | Store at -20°C | |
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1 mg | 5 mg | 10 mg | |
1 mM | 1.7993 mL | 8.9964 mL | 17.9927 mL |
5 mM | 0.3599 mL | 1.7993 mL | 3.5985 mL |
10 mM | 0.1799 mL | 0.8996 mL | 1.7993 mL |
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Selective inhibition of cullin 3 neddylation through covalent targeting DCN1 protects mice from acetaminophen-induced liver toxicity
Nat Commun 2021 May 11;12(1):2621.PMID:33976147DOI:PMC8113459
Cullin-RING E3 ligases (CRLs) regulate the turnover of approximately 20% of mammalian cellular proteins. Neddylation of individual cullin proteins is essential for the activation of each CRL. We report herein the discovery of DI-1548 and DI-1859 as two potent, selective and covalent DCN1 inhibitors. These inhibitors selectively inhibit neddylation of cullin 3 in cells at low nanomolar concentrations and are 2-3 orders of magnitude more potent than our previously reported reversible DCN1 inhibitor. Mass spectrometric analysis and co-crystal structures reveal that these compounds employ a unique mechanism of covalent bond formation with DCN1. DI-1859 induces a robust increase of NRF2 protein, a CRL3 substrate, in mouse liver and effectively protects mice from acetaminophen-induced liver damage. Taken together, this study demonstrates the therapeutic potential of selective inhibition of cullin neddylation.