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

Andrew A Guirguis; Benjamin L Ebert

doi:10.1016/j.ceb.2015.10.004

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

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

Authors

Andrew A Guirguis¹, Benjamin L Ebert²

Affiliations

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.

PMID: 26512454
DOI: 10.1016/j.ceb.2015.10.004

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Angiogenesis Inhibitors / therapeutic use*
Animals
Humans
Lenalidomide
Multiple Myeloma / drug therapy*
Multiple Myeloma / metabolism
Myelodysplastic Syndromes / drug therapy*
Myelodysplastic Syndromes / metabolism
Substrate Specificity
Thalidomide / analogs & derivatives*
Thalidomide / therapeutic use
Transcription, Genetic
Ubiquitination

Substances

Angiogenesis Inhibitors
Thalidomide
Lenalidomide

Abstract

Publication types

MeSH terms

Substances

Grants and funding