Fischer, Eric, Boehm, Kerstin, Lydeard, John R., Yang, Haidi, Stadler, Michael B., Cavadini, Simone, Nagel, Jane, Serluca-Aegerter, Fabrizio, Acker, Vincent, Lingaraju Gondichatnahalli, Manjappa, Tichkule, Ritesh, Schebesta, Michael, Forrester, William, Schirle, Markus, Hassiepen, Ulrich, Ottl, Johannes, Hild, Marc, Beckwith, Rohan, Harper, J. Wade, Jenkins, Jeremy and Thomae, Nicolas (2014) Structure of DDB1-CRBN bound to thalidomide: insights into CRL4 inhibition by small molecules. Nature.

Abstract

In the 1950s, the drug thalidomide, administered as a sedative to pregnant woman led to the birth of thousands of children with multiple defects. Despite the teratogenicity of thalidomide and its derivatives lenalidomide and pomalidomide, these immunomodulatory drugs (IMiDs) recently emerged as effective treatments for multiple myeloma and 5q-deletion-asociated dysplasia. IMiDs target the E3 ubiquitin ligase CUL4-RBX1-DDB1-CRBN (known as CRL4CRBN) and promote the ubiquitination of the IKAROS family transcription factors IKZF1 and IKZF3 by CRL4CRBN. How IMiD binding affects CRL4CRBN at the molecular level remained unclear.

Item Type:	Article
Date Deposited:	28 Apr 2016 23:45
Last Modified:	06 Jan 2017 00:45
URI:	https://oak.novartis.com/id/eprint/23136