| 规格: | 98% |
| 分子量: | 505.56 |
| 包装 | 价格(元) |
| 1mg | 电议 |
| 5mg | 电议 |
| 10mg | 电议 |
Background:
CSN5i-3 is a potent, selective and orally available inhibitor of CSN5; inhibits CSN-catalysed Cul1 deneddylation with an IC50 value of 5.8 nM.
CSN5i-3 traps CRLs in the neddylated state, which leads to inactivation of a subset of CRLs by inducing degradation of their substrate recognition module[1].
CSN5i-3 shows a good pharmacokinetic profile. CSN5i-3 inhibits growth of human xenograft. Treatment with CSN5i-3 triggers the formation of cleaved PARP and cleaved caspase 3 indicative of apoptosis induction[1].
[1]. Schlierf A, et al. Targeted inhibition of the COP9 signalosome for treatment of cancer. Nat Commun. 2016 Oct 24;7:13166.
Protocol:
Cell experiment: | Cell viability is measured using the CellTiter-Glo Assay. Cells (THP-1, HCT116, NCI-H2030 and TE-1) are treated with CSN5i-3 (1 nM, 10 nM, 100 nM, 1 μM, 10 μM) for 72 hours[1]. |
Animal experiment: | Mice[1]SU-DHL-1 xenografts were grown in SCID-bg mice and dosed by oral administration with either vehicle control or CSN5i-3 at the indicated doses (50 mg/kg BID, 100mg/kg QD) and schedules (3, 7, 10, 14 day). Tumour response is reported as percentage change in tumour volume at the last day of treatment relative to start of treatment. |
参考文献: [1]. Schlierf A, et al. Targeted inhibition of the COP9 signalosome for treatment of cancer. Nat Commun. 2016 Oct 24;7:13166. | |
m.cnreagent.com