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Curr Opin Cell Biol. 2015 Dec;37:61-7. doi: 10.1016/j.ceb.2015.10.004. Epub 2015 Nov 11.

Lenalidomide: deciphering mechanisms of action in myeloma, myelodysplastic syndrome and beyond.

Author information

1
Brigham and Women's Hospital, Division of Hematology, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
2
Brigham and Women's Hospital, Division of Hematology, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: benjamin_Ebert@dfci.harvard.edu.

Abstract

Lenalidomide and its related 'analogues' modulate the substrate specificity of the CRL4(CRBN) E3 ubiquitin ligase complex. Polyubiquitination and subsequent proteasomal degradation of IKZF1 and IKZF3 in multiple myeloma and CK1α in del(5q) MDS has recently been linked to therapeutic efficacy of this class of compounds. Harnessing ubiquitin ligase substrate specificity, may in time facilitate the degradation of other 'undruggable' proteins and allow for separation of detrimental side effects of IMiD compounds from those associated with therapeutic efficacy.

PMID:
26512454
DOI:
10.1016/j.ceb.2015.10.004
[Indexed for MEDLINE]

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