Lenalidomide
Immunomodulator / Thalidomide analog which, like thalidomide,1 binds to cereblon which is the substrate recognition component of a cullin-dependent ubiquitin ligase and inhibits its autoubiquitination activity2. Induces degradation of T-cell repressors Ikaros (IKZF1) and Aiolos (IKZF3) leading to T cell activation2. Selective inhibition of IKZF1 and IKZF3 in multiple myeloma cells results in cell death3,4. Cell permeable. Caution: Teratogenic
Biochemicals & reagents
191732-72-6
CC-5013
1) Ito et al. (2010), Identification of a primary target of thalidomide teratogenicity; Science, 327 1345 2) Gandhi et al. (2014), Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells by inducing degradation of T-cell repressors Ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4(CRBN); Br.J. Haematol., 164 811 3) Kronke et al. (2014), Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells; Science, 343 301 4) Lu et al. (2014), The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins; Science., 343 305
RT
TARGET: Ubiquitin ligase; Molecular glue -- PATHWAY: Degradation; Cytokine; TNF -- RESEARCH AREA: Immunology; Angiogenesis -- DISEASE AREA: Inflammation; Cancer