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Dingjingyu Zhou

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Articles

GPCR antagonism via rewiring of receptor trafficking and degradation

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By Kaitlin Rhee, Lawrence Shue, Akimasa Adachi, Pengwei Sun, James Osei-Owusu, Aoxing Cheng, Yi Xu, Qingyue Li, Apoorva Baluapuri, Edward Harvey, Karen Adelman, Meredith A. Skiba, Bianxiao Cui, Jun R Huh, Andrew C. Kruse, Xin Zhou, Dingjingyu Zhou
| Nature Verified
Abstract G-protein-coupled receptors (GPCRs) represent one of the most important yet incompletely addressed classes of therapeutic targets1. Here we report a strategy for functional GPCR antagonism through bispecific antibody-mediated endocytosis and lysosomal degradation. GPCR–TfR1 targeting chimeras (GTACs) achieve potent and selective downregulation of multiple GPCRs, including BILF1, RXFP1 and CCR6—viral, cancer and immune targets that have been difficult to drug2,3,4.
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