生物活性

• 靶点	TNFα IC50:13nM

• 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^[3]. 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^[4]. Lenalidomide treatment for 4 days was toxic to most ABC DLBCL cell lines^[5]. 2 μM Lenalidomide led to down regulation of IKZF1, IKZF3 and IRF4 in MM1S, KMS34 and RPMI8226 cells^[3]. 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^[6]. 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^[5].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  697	-	Growth Inhibition Assay	-	IC50=50.3545 μM	SANGER
  A2058	-	Growth Inhibition Assay	-	IC50=13.8199 μM	SANGER
  A2780	-	Growth Inhibition Assay	-	IC50=35.3601 μM	SANGER

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• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT01002703	Multiple Myeloma	Phase 1 Phase 2	Unknown	October 2014	Germany ... more >> University of Leipzig Recruiting Leipzig, Germany, 04103 Contact: Dietger Niederwieser    +4934197 ext 13050    dietger@medizin.uni-leipzig.de    Sub-Investigator: Wolfram Pönisch Collapse <<
  NCT01718743	Myeloma	Phase 2	Active, not recruiting	December 2020	United States, Texas ... more >> University of Texas MD Anderson Cancer Center Houston, Texas, United States, 77030 Collapse <<
  NCT00923234	Myelodysplastic Syndromes ... more >> Acute Myelogenous Leukemia Collapse <<	Phase 1	Terminated(The primary objecti... more >>ve has already been answered with the number of recruited patients.) Collapse <<	-	Germany ... more >> Medizinische Klinik und Poliklinik I, Uniklinik Dresden, Germany Universitätsklinikum Düsseldorf, Klinik für Hämatologie/Onkologie/klinische Immunologie Düsseldorf, Germany, 40225 Klinikum der J.W. Goethe-Universität, Medizinische Klink II Frankfurt, Germany, 60590 Technische Universität München, Klinikum Rechts der Isar München, Germany, 81675 Collapse <<

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