Front Cover: Antibody Conjugation of a Chimeric BET Degrader Enables <i>in vivo</i> Activity (ChemMedChem 1/2020)
Thomas H. Pillow, Pragya Adhikari, Robert A. Blake, Jinhua Chen, Geoffrey Del Rosario, Gauri Deshmukh, Isabel Figueroa, Karen E. Gascoigne, Amrita V. Kamath, Susan Kaufman, Tracy Kleinheinz, Katherine R. Kozak, Brandon Latifi, Douglas D. Leipold, Chun Sing Li, Ruina Li, Melinda M. Mulvihill, Aimee O’Donohue, Rebecca K. Rowntree, Jack Sadowsky, John Wai, Xinxin Wang, Cong Wu, Zijin Xu, Hui Yao, Shang‐Fan Yu, Donglu Zhang, Richard Zang, Hongyan Zhang, Hao Zhou, Xiaoyu Zhu, Peter S. Dragovich
Abstract
The Front Cover shows the intracellular delivery of a chimeric protein degrader via an antibody conjugate. The antibody–degrader conjugate is stable in circulation and, upon binding to an antigen on the cell surface, is trafficked to the lysosome. Antibody catabolism and linker cleavage subsequently release the free chimeric degrader and allow it to form a trimeric complex between a target protein and a ubiquitin ligase. This complex promotes ubiquitination of the target protein resulting in its degradation via the cellular proteasome. More information can be found in the Full Paper by Full Paper by Peter S. Dragovich, Thomas H. Pillow et al. on page 19 in Issue 1, 2020 (DOI: 10.1002/cmdc.201900497).