Yingxue Fu

1 Introduction Skeletal muscle wasting is a serious complication of many diseases and a side effect of common pharmacologic treatments but only limited therapeutic interventions are currently available. Skeletal muscle wasting associated with cancer is a component of cachexia [1], a systemic wasting syndrome that reduces the survival of cancer patients and their response to therapy [2, 3].

Abstract Proteolysis-targeting chimeras (PROTACs) containing a target protein ligand linked to an E3 ubiquitin ligase ligand induce target protein degradation through E3 recruitment. Most PROTACs bind a surface cleft of the protein of interest rather than a buried pocket. Using the nuclear receptor PXR, we previously described the inherent difficulties of PROTAC targeting via a deep solvent-inaccessible ligand binding pocket.

Conflicts of Interest The authors declare no conflicts of interest. Supporting Information Filename Description pmic70061-sup-0001-SuppMat.docx1.6 MB Supporting File 1: pmic70061-sup-0001-SuppMat.docx. References 1 and , “Mass Spectrometry-Based Proteomics,” Nature 422 (2003): 198–207, https://doi.org/10.1038/nature01511.