ArticleJournal of computer-aided molecular design2017
Structure based classification for bile salt export pump (BSEP) inhibitors using comparative structural modeling of human BSEP.
Article in Journal of computer-aided molecular design, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Integrating AI in Medicinal Chemistry for Accelerated Drug Discovery: A Comprehensive SAR (CSAR) Optimization Strategy and Discovery of Potent ALDH3A1 Inhibitors.Journal of medicinal chemistry · 2026Article
- Leveraging Consensus Docking Approaches for Human Mitochondrial Complexes I and III.Chemical research in toxicology · 2026Article
- Prediction of bile salt export pump inhibition using biomimetic chromatographic descriptors: Integrating membrane affinity and protein binding.ADMET & DMPK · 2026Article
- Integrating Mechanistic and Toxicokinetic Information in Predictive Models of Cholestasis.Journal of chemical information and modeling · 2024Article
- Ligand- and Structure-based Approaches for Transmembrane Transporter Modeling.Current drug research reviews · 2024Review
- In silico modeling-based new alternative methods to predict drug and herb-induced liver injury: A review.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2023Review
- Using a Graph Convolutional Neural Network Model to Identify Bile Salt Export Pump Inhibitors.ACS omega · 2023Article
- Using Jupyter Notebooks for re-training machine learning models.Journal of cheminformatics · 2022Article
- FXR expression in rats of hilar cholangiocarcinoma.Scientific reports · 2022Article
- HybridACS pharmacology & translational science · 2021Article
- Bsep expression in hilar cholangiocarcinoma of rat model.Scientific reports · 2021Article
- The Bile Salt Export Pump: Molecular Structure, Study Models and Small-Molecule Drugs for the Treatment of Inherited BSEP Deficiencies.International journal of molecular sciences · 2021Review
- Discovery of Potent Inhibitors for the Large Neutral Amino Acid Transporter 1 (LAT1) by Structure-Based Methods.International journal of molecular sciences · 2018Article
- Can Bile Salt Export Pump Inhibition Testing in Drug Discovery and Development Reduce Liver Injury Risk? An International Transporter Consortium Perspective.Clinical pharmacology and therapeutics · 2018Review
- Interspecies comparison of putative ligand binding sites of human, rat and mouse P-glycoprotein.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2018Article
- In silico toxicology: From structure-activity relationships towards deep learning and adverse outcome pathways.Wiley interdisciplinary reviews. Computational molecular scienceReview
- NTCP Change in Rats of Hilar Cholangiocarcinoma and Therapeutic Significance.Technology in cancer research & treatmentArticle
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The bile salt export pump (BSEP) actively transports conjugated monovalent bile acids from the hepatocytes into the bile. This facilitates the formation of micelles and promotes digestion and absorption of dietary fat. Inhibition of BSEP leads to decreased bile flow and accumulation of cytotoxic bile salts in the liver. A number of compounds have been identified to interact with BSEP, which results in drug-induced cholestasis or liver injury. Therefore, in silico approaches for flagging compounds as potential BSEP inhibitors would be of high value in the early stage of the drug discovery pipeline. Up to now, due to the lack of a high-resolution X-ray structure of BSEP, in silico based identification of BSEP inhibitors focused on ligand-based approaches. In this study, we provide a homology model for BSEP, developed using the corrected mouse P-glycoprotein structure (PDB ID: 4M1M). Subsequently, the model was used for docking-based classification of a set of 1212 compounds (405 BSEP inhibitors, 807 non-inhibitors). Using the scoring function ChemScore, a prediction accuracy of 81% on the training set and 73% on two external test sets could be obtained. In addition, the applicability domain of the models was assessed based on Euclidean distance. Further, analysis of the protein-ligand interaction fingerprints revealed certain functional group-amino acid residue interactions that could play a key role for ligand binding. Though ligand-based models, due to their high speed and accuracy, remain the method of choice for classification of BSEP inhibitors, structure-assisted docking models demonstrate reasonably good prediction accuracies while additionally providing information about putative protein-ligand interactions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.