Prediction Model With High-Performance Constitutive Androstane Receptor (CAR) Using DeepSnap-Deep Learning Approach From the Tox21 10K Compound Library

Int J Mol Sci. 2019 Sep 30;20(19):4855. doi: 10.3390/ijms20194855.


The constitutive androstane receptor (CAR) plays pivotal roles in drug-induced liver injury through the transcriptional regulation of drug-metabolizing enzymes and transporters. Thus, identifying regulatory factors for CAR activation is important for understanding its mechanisms. Numerous studies conducted previously on CAR activation and its toxicity focused on in vivo or in vitro analyses, which are expensive, time consuming, and require many animals. We developed a computational model that predicts agonists for the CAR using the Toxicology in the 21st Century 10k library. Additionally, we evaluate the prediction performance of novel deep learning (DL)-based quantitative structure-activity relationship analysis called the DeepSnap-DL approach, which is a procedure of generating an omnidirectional snapshot portraying three-dimensional (3D) structures of chemical compounds. The CAR prediction model, which applies a 3D structure generator tool, called CORINA-generated and -optimized chemical structures, in the DeepSnap-DL demonstrated better performance than the existing methods using molecular descriptors. These results indicate that high performance in the prediction model using the DeepSnap-DL approach may be important to prepare suitable 3D chemical structures as input data and to enable the identification of modulators of the CAR.

Keywords: DeepSnap; QSAR; Tox21; chemical structure; constitutive androgen receptor (CAR); deep learning.

MeSH terms

  • Algorithms
  • Deep Learning*
  • Drug Discovery* / methods
  • Ligands
  • Quantitative Structure-Activity Relationship*
  • Receptors, Cytoplasmic and Nuclear / agonists
  • Receptors, Cytoplasmic and Nuclear / chemistry*
  • Reproducibility of Results
  • Small Molecule Libraries


  • Ligands
  • Receptors, Cytoplasmic and Nuclear
  • Small Molecule Libraries
  • constitutive androstane receptor