2. Academic Validation
  3. Development of 3D-QSAR models for predicting the activities of chemicals to stimulate muscle growth via β2-adrenoceptor

Development of 3D-QSAR models for predicting the activities of chemicals to stimulate muscle growth via β2-adrenoceptor

  • Toxicol In Vitro. 2021 Dec;77:105251. doi: 10.1016/j.tiv.2021.105251.
Shuyu Ouyang 1,  Dachuan Zhang 2,  Tengfei Zhu 1,  Shuting Yu 1,  Wunier 1,  Qian-Nan Hu 3,  Yingying Le 4
Affiliations

Affiliations

  • 1 CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
  • 2 CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
  • 3 CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: [email protected].
  • 4 CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing 100021, China. Electronic address: [email protected].
PMID: 34601065 DOI: 10.1016/j.tiv.2021.105251
Abstract

β2-adrenoceptor (β2AR) agonists can stimulate skeletal muscle growth. Their illegal use in food-producing Animals, human athletes and bodybuilders causes adverse health effects. In the present study, we developed 3D-QSAR models for predicting the activity of chemicals which can stimulate skeletal muscle growth through β2AR. The activity of 25 β2AR agonists was measured by β2AR-cAMP response element (CRE) -luciferase (Luc) reporter assay. The 3D-QSAR models were built using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The CoMFA and CoMSIA models displayed high external predictability (R2 0.996 and 0.992, respectively) and good statistical robustness, and revealed that electrostatic effects were the most prominent forces influencing the activity of β2AR agonists. The CoMFA and CoMSIA contour plots provided clues regarding the main chemical features responsible for the activity variations and also resulted in predictions which correlate very well with the observed activity. In vitro study with differentiated myotubes showed that the potency orders of β2AR agonists in activating the β2AR-CRE-Luc reporter and in upregulating CREB target genes related to muscle growth were consistent. These 3D-QSAR models provide tools for predicting the activity of chemicals which might be illegally used in livestock or humans to stimulate skeletal muscle growth.

Keywords

3D-QSAR models; CRE-luciferase reporter; CoMFA; CoMSIA; Myotube gene expression; β(2)AR agonists.

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