货号：L1280

储存条件：粉末-20°C可保存3年。

产品描述

Cereblon, encoded by CRBN gene, is the substrate recognition component of a DCX (DDB1-CUL4-X-box) E3 protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Cereblon, or the E3 ligase complex mediated normal degradation of key regulatory proteins is required for normal limb outgrowth and expression of the fibroblast growth factor FGF8. They may play a role in memory and learning by regulating the assembly and neuronal surface expression of large-conductance calcium-activated potassium channels in brain regions involved in memory and learning via its interaction with KCNT1. It was well reported that binding of thalidomide-related drugs, such as Lenalidomide, changed the substrate specificity of the E3 ligase complex, leading to decreased degradation of MEIS2 and other target proteins and increased degradation of MYC, IRF4, IKZF1 and IKZF3. Lenalidomide is an analogue of thalidomide with immunomodulatory, antiangiogenic, and antineoplastic properties. The cellular target of lenalidomide is cereblon. Another experiment revealed that Lenalidomide down regulated IKZF1 and IKZF3 and this was cereblon-dependent. Lenalidomide treatment for 4 days was toxic to most ABC DLBCL cell lines. 2 μM Lenalidomide led to down regulation of IKZF1, IKZF3 and IRF4 in MM1S, KMS34 and RPMI8226 cells. In a MM1S xenograft model in CB17-SCID mice, Lenalidomide was administrated at the dose of 15 mg/kg i.p. 5days weekly as a single agent or in combination. The results were Lenalidomide was marginally effective as a single agent and the combination of Lenalidomide with dexamethasone or the triple combination of Lenalidomide, dexamethasone and panobinostat. In an OCI-Ly10 xenograft model, daily i.p. treatment with lenalidomide at the dose of 10 mg/kg for 20 days resulted in little effect as a single agent but effective in combination with ibrutinib.

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