Researchers developed an antagonist nanobody targeting the oxytocin receptor that produces a tocolytic effect in mice, Nature Communications reported on September 11, 2026. The research team used artificial intelligence-driven protein design to screen nanobodies against the receptor, a primary target for preterm birth treatments.
Preterm birth is defined as delivery before 37 completed weeks of gestation. It creates risks to maternal and neonatal health, including neonatal respiratory distress syndrome, intraventricular hemorrhage, long-term developmental challenges, and death. Pharmaceutical research has targeted G protein-coupled receptor (GPCR) mediation to suppress uterine contractions, but conventional GPCR treatments rely on small molecules. These small molecules often cross the placental barrier and carry risks of fetal toxicity. In contrast, antibody therapies exhibit minimal cell membrane permeability.
Screening identified several nanobodies with antagonist activity against the oxytocin receptor. One nanobody demonstrated antagonist activity comparable to Atosiban, a drug used in clinical settings, while showing higher subtype selectivity. Pharmacological and structural analyses revealed that the nanobody uses mechanisms distinct from those found in small molecule antagonists.
Co-first authors Jia Nie, Kaixuan Gao, and Xin Zhang conducted the study across institutions including Xiangya Hospital Central South University, Tsinghua University, and the Women and Children’s Hospital of Chongqing Medical University. Collaborators A. C. Kruse of Harvard University and A. Manglik of the University of California San Francisco supplied the synthetic nanobody library used during the screening.
Six researchers—Nie, Gao, Zhang, Weishe Zhang, Xiangyu Liu, and Lijuan Liu—filed patent application number 202510223101.3 based on the findings. Project funding came from the National Natural Science Foundation of China, the Beijing Frontier Research Center for Biological Structure, and the Tsinghua-Peking Center for Life Sciences.
