The binding of palonosetron and other antiemetic drugs to the serotonin 5-HT3 receptor. Inaccurately perceived as niche drugs, antiemetics are key elements of cancer treatment alleviating the most dreaded side effect of chemotherapy. Serotonin 5-HT3 receptor antagonists are the most commonly prescribed class of drugs to control chemotherapy-induced nausea and vomiting. These antagonists have been clinically successful drugs since the 1980s, yet our understanding of how they operate at the molecular level has been hampered by the difficulty of obtaining structures of drug-receptor complexes. Here, we report the cryoelectron microscopy structure of the palonosetron-bound 5-HT3 receptor. We investigate the binding of palonosetron, granisetron, dolasetron, ondansetron, and cilansetron using molecular dynamics, covering the whole set of antagonists used in clinical practice. The structural and computational results yield detailed atomic insight into the binding modes of the drugs. In light of our data, we establish a comprehensive framework underlying the inhibition mechanism by the -setron drug family. Structure, 2020.

Recent publications

Structure, substrate binding and symmetry of the mitochondrial ADP/ATP carrier in its matrix-open state
Joel Jose Montalvo-Acosta; Edmund R.S. Kunji; Jonathan J. Ruprecht; Francois Dehez; Christophe Chipot;
Biophysical Journal (2021)
Accurate Description of Cation-π Interactions in Proteins with a Nonpolarizable Force Field at No Additional Cost
Han Liu; Haohao Fu; Xueguang Shao; Wensheng Cai; Christophe Chipot;
Journal of Chemical Theory and Computation (2020) 31 (10): 671-6407
Cryo-EM and MD infer water-mediated proton transport and autoinhibition mechanisms of V
Soung-Hun Roh; Mrinal Shekhar; Grigore Pintilie; Christophe Chipot; Stephan Wilkens; Abhishek Singharoy; Wah Chiu;
Science Advances (2020) 10 (41): 5276-


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