ArticleScientific reports2023
Structure-based discovery of novel P-glycoprotein inhibitors targeting the nucleotide binding domains.
Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- Breaking the Efflux Barrier: P-Glycoprotein and Emerging Strategies to Overcome Multidrug Resistance in Cancer.Cancers · 2026Review
- The Antidepressant Drug Clomipramine Inhibits the ABC Transporter BmrA.Chembiochem : a European journal of chemical biology · 2026Article
- (N)-Methanocarba Adenosine Derivatives as Dual Modulators of P-Glycoprotein and ABCG2 Transporters.Journal of medicinal chemistry · 2026Article
- Advanced strategies to overcome multidrug resistance in cancer therapy: progress in P-glycoprotein inhibitors, drug delivery, and personalized medicine.Investigational new drugs · 2025Review
- Allosteric Inhibition of P-Glycoprotein-Mediated Efflux by DMH1.Biomedicines · 2025Article
- Influence of Tariquidar, an ABC Transporter Inhibitor, on the CaPharmaceuticals (Basel, Switzerland) · 2025Article
- From blood vessels to brain cells: Connecting the circulatory system and Parkinson's disease.Journal of Parkinson's disease · 2025Review
- The Advancements of Marine Natural Products in the Treatment of Alzheimer's Disease: A Study Based on Cell and Animal Experiments.Marine drugs · 2025Review
- Article
- 8-Prenylgenistein Isoflavone in Cheonggukjang Acts as a Novel AMPK Activator Attenuating Hepatic Steatosis by Enhancing the SIRT1-Mediated Pathway.International journal of molecular sciences · 2024Article
- Exploring Amino Acid Transporters as Therapeutic Targets for Cancer: An Examination of Inhibitor Structures, Selectivity Issues, and Discovery Approaches.Pharmaceutics · 2024Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
P-glycoprotein (P-gp), a membrane transport protein overexpressed in certain drug-resistant cancer cells, has been the target of numerous drug discovery projects aimed at overcoming drug resistance in cancer. Most characterized P-gp inhibitors bind at the large hydrophobic drug binding domain (DBD), but none have yet attained regulatory approval. In this study, we explored the potential of designing inhibitors that target the nucleotide binding domains (NBDs), by computationally screening a large library of 2.6 billion synthesizable molecules, using a combination of machine learning-guided molecular docking and molecular dynamics (MD). 14 of the computationally best-scoring molecules were subsequently tested for their ability to inhibit P-gp mediated calcein-AM efflux. In total, five diverse compounds exhibited inhibitory effects in the calcein-AM assay without displaying toxicity. The activity of these compounds was confirmed by their ability to decrease the verapamil-stimulated ATPase activity of P-gp in a subsequent assay. The discovery of these five novel P-gp inhibitors demonstrates the potential of in-silico screening in drug discovery and provides a new stepping point towards future potent P-gp inhibitors.
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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.