ArticleBioorganic & medicinal chemistry letters2012
Further optimization of the K-Cl cotransporter KCC2 antagonist ML077: development of a highly selective and more potent in vitro probe.
Article in Bioorganic & medicinal chemistry letters, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
53 citing papers in PubMed.
- Presynaptic chloride-dependent regulation of spontaneous glutamate release in the rat medial preoptic nucleus.Frontiers in cellular neuroscience · 2026Article
- Article
- Exploring the Cell Biological and Functional Effects of the First Disease Associated KCC1 Genetic Variant.Journal of cellular physiology · 2025Article
- Biophysical characterization and ion transport with cell-based and proteoliposome reconstitution assays of invertebrate KFEBS open bio · 2025Article
- Intraventricular haemorrhage in premature infants: the role of immature neuronal salt and water transport.Brain : a journal of neurology · 2024Article
- Optogenetic Determination of Dynamic and Cell-Type-Specific Inhibitory Reversal Potentials.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- The brain-specific kinase LMTK3 regulates neuronal excitability by decreasing KCC2-dependent neuronal CliScience · 2024Article
- Constitutive KCC2 Cell- and Synapse-Specifically Regulates NMDA Receptor Activity in the Spinal Cord.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Neuronal KActa pharmacologica Sinica · 2024Review
- Pharmacology of Compounds Targeting Cation-Chloride Cotransporter Physiology.Handbook of experimental pharmacology · 2024Article
- Development of KCC2 therapeutics to treat neurological disorders.Frontiers in molecular neuroscience · 2024Article
- The role ofJournal of pharmaceutical analysis · 2023Review
- Restoring neuronal chloride extrusion reverses cognitive decline linked to Alzheimer's disease mutations.Brain : a journal of neurology · 2023Article
- Article
- KCC2 reverse mode helps to clear postsynaptically released potassium at glutamatergic synapses.Cell reports · 2023Article
- Delaying the GABA Shift Indirectly Affects Membrane Properties in the Developing Hippocampus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Structure of the human cation-chloride cotransport KCC1 in an outward-open state.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Inhibiting with-no-lysine kinases enhances K+/Cl- cotransporter 2 activity and limits status epilepticus.Brain : a journal of neurology · 2022Article
- Discovery of Small Molecule KCC2 Potentiators Which AttenuateFrontiers in cell and developmental biology · 2022Article
- The role of GABAergic signalling in neurodevelopmental disorders.Nature reviews. Neuroscience · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
Further chemical optimization of the MLSCN/MLPCN probe ML077 (KCC2 IC(50)=537 nM) proved to be challenging as the effort was characterized by steep SAR. However, a multi-dimensional iterative parallel synthesis approach proved productive. Herein we report the discovery and SAR of an improved novel antagonist (VU0463271) of the neuronal-specific potassium-chloride cotransporter 2 (KCC2), with an IC(50) of 61 nM and >100-fold selectivity versus the closely related Na-K-2Cl cotransporter 1 (NKCC1) and no activity in a larger panel of GPCRs, ion channels and transporters.
Indexed as
Identifiers
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.