ArticleCell chemical biology2019
Zinc-Chelating Small Molecules Preferentially Accumulate and Function within Pancreatic β Cells.
Article in Cell chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- Mechanistic insights and approaches for beta cell regeneration.Nature chemical biology · 2025Review
- Zinc-chelating BET bromodomain inhibitors equally target islet endocrine cell types.American journal of physiology. Regulatory, integrative and comparative physiology · 2024Article
- Mobile zinc as a modulator of sensory perception.FEBS letters · 2023Review
- Unusual Reactivity and Metal Affinity of Water-Soluble Dipyrrins.Inorganic chemistry · 2022Article
- β-Cell Succinate Dehydrogenase Deficiency Triggers Metabolic Dysfunction and Insulinopenic Diabetes.Diabetes · 2022Article
- Small-molecule discovery in the pancreatic beta cell.Current opinion in chemical biology · 2022Review
- Induction of Cell Death in Pancreatic Tumors by Zinc and Its Fluorescence Chelator TSQ.Biological trace element research · 2022Article
- Targeting Small GTPases and Their Prenylation in Diabetes Mellitus.Journal of medicinal chemistry · 2021Review
- Harnessing reaction-based probes to preferentially target pancreatic β-cells and β-like cells.Life science alliance · 2021Article
- Protocol for determining zinc-dependent β cell-selective small-molecule delivery in mouse pancreas.STAR protocols · 2021Article
- Human Beta Cell Regenerative Drug Therapy for Diabetes: Past Achievements and Future Challenges.Frontiers in endocrinology · 2021Review
- Protective role of biosynthesised zinc oxide nanoparticles on pancreatic beta cells: an in vitro and in vivo approach.IET nanobiotechnology · 2020Article
- Native Zinc Catalyzes Selective and Traceless Release of Small Molecules in β-Cells.Journal of the American Chemical Society · 2020Article
- Generation of highly potent DYRK1A-dependent inducers of human β-Cell replication via Multi-Dimensional compound optimization.Bioorganic & medicinal chemistry · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Diabetes is a hyperglycemic condition characterized by pancreatic β-cell dysfunction and depletion. Whereas methods for monitoring β-cell function in vivo exist, methods to deliver therapeutics to β cells are lacking. We leveraged the rare ability of β cells to concentrate zinc to preferentially trap zinc-binding molecules within β cells, resulting in β-cell-targeted compound delivery. We determined that zinc-rich β cells and islets preferentially accumulated TSQ (6-methoxy-8-p-toluenesulfonamido-quinoline) in a zinc-dependent manner compared with exocrine pancreas. Next, we asked whether appending a zinc-chelating moiety onto a β-cell replication-inducing compound was sufficient to confer preferential β-cell accumulation and activity. Indeed, the hybrid compound preferentially accumulated within rodent and human islets in a zinc-dependent manner and increased the selectivity of replication-promoting activity toward β cells. These data resolve the fundamental question of whether intracellular accumulation of zinc-chelating compounds is influenced by zinc content. Furthermore, application of this principle yielded a proof-of-concept method for β-cell-targeted drug delivery and bioactivity.
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What OpenQuestion holds
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.