ArticleProceedings of the National Academy of Sciences of the United States of America2011
A small molecule differentiation inducer increases insulin production by pancreatic β cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 44 citations in OpenAlex.
- Small molecule-mediated activation of Notch signal transduction.Cell death & disease · 2026Article
- Neurogenic inducers inhibit the proliferation of pancreatic cancer by promoting tumor cell transdifferentiation.Journal of experimental & clinical cancer research : CR · 2025Article
- Signal transduction pathways controllingiScience · 2025Article
- Tumor-suppressive disruption of cancer subtype-associated super enhancer circuits by small molecule treatment.NAR cancer · 2023Article
- MRTF specifies a muscle-like contractile module in Porifera.Nature communications · 2022Article
- Calcineurin/NFATc2 and PI3K/AKT signaling maintains β-cell identity and function during metabolic and inflammatory stress.iScience · 2022Article
- Chemical combinations potentiate human pluripotent stem cell-derived 3D pancreatic progenitor clusters toward functional β cells.Nature communications · 2021Article
- Activation of Cilia-Independent Hedgehog/GLI1 Signaling as a Novel Concept for Neuroblastoma Therapy.Cancers · 2021Article
- Concerted cell and in vivo screen for pancreatic ductal adenocarcinoma (PDA) chemotherapeutics.Scientific reports · 2020Article
- ISX-9 manipulates endocrine progenitor fate revealing conserved intestinal lineages in mouse and human organoids.Molecular metabolism · 2020Article
- Rapid and Efficient Conversion of Human Fibroblasts into Functional Neurons by Small Molecules.Stem cell reports · 2019Article
- GPR68: An Emerging Drug Target in Cancer.International journal of molecular sciences · 2019Review
- Isx9 Regulates Calbindin D28K Expression in Pancreatic β Cells and Promotes β Cell Survival and Function.International journal of molecular sciences · 2018Article
- Isoxazole Alters Metabolites and Gene Expression, Decreasing Proliferation and Promoting a Neuroendocrine Phenotype in β-Cells.ACS chemical biology · 2016Article
- Activation of MRTF-A-dependent gene expression with a small molecule promotes myofibroblast differentiation and wound healing.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Chromatin-tethered MAPKs.Current opinion in cell biology · 2013Review
- Functional and mechanistic exploration of an adult neurogenesis-promoting small molecule.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2012Article
- Coupling hippocampal neurogenesis to brain pH through proneurogenic small molecules that regulate proton sensing G protein-coupled receptors.ACS chemical neuroscience · 2012Article
- Regulated expression of pH sensing G Protein-coupled receptor-68 identified through chemical biology defines a new drug target for ischemic heart disease.ACS chemical biology · 2012Article
- Targeting native adult heart progenitors with cardiogenic small molecules.ACS chemical biology · 2012Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
New drugs for preserving and restoring pancreatic β-cell function are critically needed for the worldwide epidemic of type 2 diabetes and the cure for type 1 diabetes. We previously identified a family of neurogenic 3,5-disubstituted isoxazoles (Isx) that increased expression of neurogenic differentiation 1 (NeuroD1, also known as BETA2); this transcription factor functions in neuronal and pancreatic β-cell differentiation and is essential for insulin gene transcription. Here, we probed effects of Isx on human cadaveric islets and MIN6 pancreatic β cells. Isx increased the expression and secretion of insulin in islets that made little insulin after prolonged ex vivo culture and increased expression of neurogenic differentiation 1 and other regulators of islet differentiation and insulin gene transcription. Within the first few hours of exposure, Isx caused biphasic activation of ERK1/2 and increased bulk histone acetylation. Although there was little effect on histone deacetylase activity, Isx increased histone acetyl transferase activity in nuclear extracts. Reconstitution assays indicated that Isx increased the activity of the histone acetyl transferase p300 through an ERK1/2-dependent mechanism. In summary, we have identified a small molecule with antidiabetic activity, providing a tool for exploring islet function and a possible lead for therapeutic intervention in diabetes.
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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.