ReviewAmerican journal of physiology. Cell physiology2021
Advances in the development of novel compounds targeting cation-chloride cotransporter physiology.
Review in American journal of physiology. Cell physiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- Regulated degradation of KCC2, a potassium-chloride co-transporter required for synaptic transmission and neurodevelopment.Channels (Austin, Tex.) · 2026Review
- "Molecular Shakers" as Transmembrane Single-Molecule Channels Toward 1:1 ClAngewandte Chemie (International ed. in English) · 2026Article
- Novel voltage-dependent ClNeuroscience letters · 2025Article
- New epilepsy therapies in development.Nature reviews. Drug discovery · 2024Review
- Engineering the ChlorON Series: Turn-On Fluorescent Protein Sensors for Imaging Labile Chloride in Living Cells.ACS central science · 2024Article
- Therapeutic potential for KCC2-targeted neurological diseases.The Japanese dental science review · 2023Review
- Outcomes of the 2019 hydrocephalus association workshop, "Driving common pathways: extending insights from posthemorrhagic hydrocephalus".Fluids and barriers of the CNS · 2023Review
- Structural Pharmacology of Cation-Chloride Cotransporters.Membranes · 2022Review
- The erythroid K-Cl cotransport inhibitor [(dihydroindenyl)oxy]acetic acid blocks erythroid CaAmerican journal of physiology. Cell physiology · 2022Article
- Chloride channels with ClC-1-like properties differentially regulate the excitability of dopamine receptor D1- and D2-expressing striatal medium spiny neurons.American journal of physiology. Cell physiology · 2022Article
- Novel cell lines derived from Chinese hamster kidney tissue.PloS one · 2022Article
- Glial Chloride Homeostasis Under Transient Ischemic Stress.Frontiers in cellular neuroscience · 2021Article
- The biogenesis of potassium transporters: implications of disease-associated mutations.Critical reviews in biochemistry and molecular biologyReview
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
For about half a century, the pharmacology of electroneutral cation-chloride cotransporters has been dominated by a few drugs that are widely used in clinical medicine. Because these diuretic drugs are so good at what they do, there has been little incentive in expanding their pharmacology. The increasing realization that cation-chloride cotransporters are involved in many other key physiological processes and the knowledge that different tissues express homologous proteins with matching transport functions have rekindled interest in drug discovery. This review summarizes the methods available to assess the function of these transporters and describe the multiple efforts that have made to identify new compounds. We describe multiple screens targeting KCC2 function and one screen designed to find compounds that discriminate between NKCC1 and NKCC2. Two of the KCC2 screens identified new inhibitors that are 3-4 orders of magnitude more potent than furosemide. Additional screens identified compounds that purportedly increase cell surface expression of the cotransporter, as well as several FDA-approved drugs that increase KCC2 transcription and expression. The technical details of each screen biased them toward specific processes in the life cycle of the transporter, making these efforts independent and complementary. In addition, each drug discovery effort contributes to our understanding of the biology of the cotransporters.
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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.