CC-122, a pleiotropic pathway modifier, mimics an interferon response and has antitumor activity in DLBCL

ABSTRACT: Cereblon (CRBN), a substrate receptor of the E3 ubiquitin ligase complex CRL4CRBN, is the target of the immunomodulatory drugs lenalidomide and pomalidomide. Recently, it was demonstrated that binding of these drugs to CRBN promotes the ubiquitination and subsequent degradation of two common substrates, transcription factors Aiolos and Ikaros. Here we report that the pleiotropic pathway modifier CC-122, a new chemical entity termed pleiotropic pathway modifier binds CRBN and promotes degradation of Aiolos and Ikaros in diffuse large B-cell lymphoma (DLBCL) and T cells in vitro, in vivo and in patients, resulting in both cell autonomous as well as immunostimulatory effects. In DLBCL cell lines, CC-122-induced degradation or shRNA mediated knockdown of Aiolos and Ikaros correlates with incre

ORGANISM(S): Homo sapiens

SUBMITTER: Anita Gandhi 

PROVIDER: E-GEOD-75420 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress