ArticlePloS one2018
Discovery of novel multidrug resistance protein 4 (MRP4) inhibitors as active agents reducing resistance to anticancer drug 6-Mercaptopurine (6-MP) by structure and ligand-based virtual screening.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Bis-(di-4-phenyl-benzylaminethiocarbonyl)disulfide sensitizes ABCC2/ALDH3A1 overexpressing NSCLC cells to cisplatin.Cancer biology & therapy · 2026Article
- A Novel Protocol for Culturing Polarized Proximal Tubular Epithelial Cells from Kidney Biopsies: Enhancing Platforms for Drug Excretion and Nephrotoxicity Studies.Journal of xenobiotics · 2025Article
- Maternal and Fetal Expression of ATP-Binding Cassette and Solute Carrier Transporters Involved in the Brain Disposition of Drugs.Advances in experimental medicine and biology · 2023Article
- Cellular Uptake and Transport Mechanism of 6-Mercaptopurine Nanomedicines for Enhanced Oral Bioavailability.International journal of nanomedicine · 2023Article
- Progress and challenges of multidrug resistance proteins in diseases.American journal of cancer research · 2022Review
- A multi-reference poly-conformational method forPeerJ · 2022Article
- Novel Symmetrical Cage Compounds as Inhibitors of the Symmetrical MRP4-Efflux Pump for Anticancer Therapy.International journal of molecular sciences · 2021Article
- Study of Endogen Substrates, Drug Substrates and Inhibitors Binding Conformations on MRP4 and Its Variants by Molecular Docking and Molecular Dynamics.Molecules (Basel, Switzerland) · 2021Article
- ABC transporter superfamily. An updated overview, relevance in cancer multidrug resistance and perspectives with personalized medicine.Molecular biology reports · 2021Review
- Scaffold fragmentation and substructure hopping reveal potential, robustness, and limits of computer-aided pattern analysis (C@PA).Computational and structural biotechnology journal · 2021Article
- Discovery of Novel Symmetrical 1,4-Dihydropyridines as Inhibitors of Multidrug-Resistant Protein (MRP4) Efflux Pump for Anticancer Therapy.Molecules (Basel, Switzerland) · 2020Article
- The Role of Eicosanoids in Gynecological Malignancies.Frontiers in pharmacology · 2020Review
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multidrug resistance protein 4 (MRP4/ABCC4) is an ATP-binding cassette (ABC) transporter. It is associated with multidrug resistance (MDR), which is becoming a growing challenge to the treatment of cancer and infections. In the context of several types of cancer in which MRP4 is overexpressed, MRP4 inhibition manifests striking effects against cancer progression and drug resistance. In this study, we combined ligand-based and structure-based drug design strategy, by searching the SPECS chemical library to find compounds that are most likely to bind to MRP4. Clustering analysis based on a two-dimensional fingerprint was performed to help with visual selection of potential compounds. Cell viability assays with potential inhibitors and the anticancer drug 6-MP were carried out to identify their bioactivity. As a result, 39 compounds were tested and seven of them reached inhibition above 55% with 6-MP. Then compound Cpd23 was discovered to improve HEK293/MRP4 cell sensibility to 6-MP dramatically, and low concentration Cpd23 (5 μM) achieved the equivalent effect of 50 μM MK571. The accumulation of 6-MP was determined by validated high-performance liquid chromatography methods, and pretreatment of the HEK293/MRP4 cells with 50 μM MK571 or Cpd23 resulted in significantly increased accumulation of 6-MP by approximately 1.5 times. This compound was first reported with a novel scaffold compared with previously known MRP4 inhibitors, which is a hopeful molecular tool that can be used for overcoming multidrug resistance research.
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