ArticleInternational journal of molecular sciences2020
Chemical Starting Matter for HNF4α Ligand Discovery and Chemogenomics.
Article in International journal of molecular sciences, 2020. 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, 23 citations in OpenAlex.
- An Activator of Tailless' Repressor Function Stimulates Anti-Neurodegenerative Gene Expression.Journal of medicinal chemistry · 2026Article
- Systematic Optimization of Fragment TLX Ligands toward Agonism and Inverse Agonism.Journal of medicinal chemistry · 2026Article
- The metabolic dysfunction-associated steatohepatitis (MASH) drug resmetirom exhibits broad nuclear receptor activity with minimal functional impact.Scientific reports · 2026Article
- Comparative Profiling and Chemogenomics Application of Chemical Tools for NR4A Nuclear Receptors.Journal of medicinal chemistry · 2025Article
- Comparative Evaluation and Profiling of Chemical Tools for the Nuclear Hormone Receptor Family 2.ACS pharmacology & translational science · 2025Article
- Chemogenomics for steroid hormone receptors (NR3).Communications chemistry · 2025Article
- Chemogenomics for NR1 nuclear hormone receptors.Nature communications · 2024Article
- Development of a Potent Nurr1 Agonist Tool for In Vivo Applications.Journal of medicinal chemistry · 2023Article
- HNF4α in Hepatocyte Health and Disease.Seminars in liver disease · 2023Review
- Druggability Evaluation of the Neuron Derived Orphan Receptor (NOR-1) Reveals Inverse NOR-1 Agonists.ChemMedChem · 2022Article
- Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Hepatocyte nuclear factor 4α (HNF4α) is a ligand-sensing transcription factor and presents as a potential drug target in metabolic diseases and cancer. In humans, mutations in the HNF4α gene cause maturity-onset diabetes of the young (MODY), and the elevated activity of this protein has been associated with gastrointestinal cancers. Despite the high therapeutic potential, available ligands and structure-activity relationship knowledge for this nuclear receptor are scarce. Here, we disclose a chemically diverse collection of orthogonally validated fragment-like activators as well as inverse agonists, which modulate HNF4α activity in a low micromolar range. These compounds demonstrate the druggability of HNF4α and thus provide a starting point for medicinal chemistry as well as an early tool for chemogenomics.
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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.