ArticlePain2019
Targeting the CaVα-CaVβ interaction yields an antagonist of the N-type CaV2.2 channel with broad antinociceptive efficacy.
Article in Pain, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Antinociceptive Activity of Chemical Components of Essential Oils That Involves Docking Studies: A Review.Frontiers in pharmacology · 2020Pooled it
- Human α1-Antitrypsin Inhibits Nociceptor Excitability and Relieves Inflammatory and Neuropathic Pain.Biomolecules · 2026Article
- Nociceptor-enriched CAPS1 isoform couples to CabioRxiv : the preprint server for biology · 2026Article
- Tumor-infiltrating nerves: unraveling the role of cancer neuroscience in tumorigenesis, disease progression, and emerging therapies.Discover oncology · 2025Review
- Voltage-Gated Ion Channels in Neuropathic Pain Signaling.Life (Basel, Switzerland) · 2025Review
- Harnessing Deep Learning Methods for Voltage-Gated Ion Channel Drug Discovery.Physiology (Bethesda, Md.) · 2025Review
- Peripheral CaeNeuro · 2024Article
- Peripheral CabioRxiv : the preprint server for biology · 2024Article
- Peptide and Peptidomimetic Inhibitors Targeting the Interaction of Collapsin Response Mediator Protein 2 with the N-Type Calcium Channel for Pain Relief.ACS pharmacology & translational science · 2024Review
- Interleukin-1α links peripheral CaScientific reports · 2024Article
- Interleukin-1α links peripheral CabioRxiv : the preprint server for biology · 2024Article
- A novel approach to completely alleviate peripheral neuropathic pain in human patients: insights from preclinical data.Frontiers in neuroanatomy · 2024Review
- A peptidomimetic modulator of the CaProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Current Drug Development Overview: Targeting Voltage-Gated Calcium Channels for the Treatment of Pain.International journal of molecular sciences · 2023Review
- Role of ion channels in the mechanism of proteinuria (Review).Experimental and therapeutic medicine · 2023Review
- Selective posttranslational inhibition of CaNature communications · 2022Article
- Targeted ubiquitination of sensory neuron calcium channels reduces the development of neuropathic pain.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Voltage-dependent CaPflugers Archiv : European journal of physiology · 2022Review
- Comparison of quinazoline and benzoylpyrazoline chemotypes targeting the CaVα-β interaction as antagonists of the N-type CaV2.2 channel.Channels (Austin, Tex.) · 2021Article
- Chemotherapy-Induced Peripheral Neuropathy: Mechanisms and Therapeutic Avenues.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 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
19 authors at 6 institutions in 3 countries.
Funding
Abstract
Inhibition of voltage-gated calcium (CaV) channels is a potential therapy for many neurological diseases including chronic pain. Neuronal CaV1/CaV2 channels are composed of α, β, γ and α2δ subunits. The β subunits of CaV channels are cytoplasmic proteins that increase the surface expression of the pore-forming α subunit of CaV. We targeted the high-affinity protein-protein interface of CaVβ's pocket within the CaVα subunit. Structure-based virtual screening of 50,000 small molecule library docked to the β subunit led to the identification of 2-(3,5-dimethylisoxazol-4-yl)-N-((4-((3-phenylpropyl)amino)quinazolin-2-yl)methyl)acetamide (IPPQ). This small molecule bound to CaVβ and inhibited its coupling with N-type voltage-gated calcium (CaV2.2) channels, leading to a reduction in CaV2.2 currents in rat dorsal root ganglion sensory neurons, decreased presynaptic localization of CaV2.2 in vivo, decreased frequency of spontaneous excitatory postsynaptic potentials and miniature excitatory postsynaptic potentials, and inhibited release of the nociceptive neurotransmitter calcitonin gene-related peptide from spinal cord. IPPQ did not target opioid receptors nor did it engage inhibitory G protein-coupled receptor signaling. IPPQ was antinociceptive in naive animals and reversed allodynia and hyperalgesia in models of acute (postsurgical) and neuropathic (spinal nerve ligation, chemotherapy- and gp120-induced peripheral neuropathy, and genome-edited neuropathy) pain. IPPQ did not cause akinesia or motor impairment, a common adverse effect of CaV2.2 targeting drugs, when injected into the brain. IPPQ, a quinazoline analog, represents a novel class of CaV2.2-targeting compounds that may serve as probes to interrogate CaVα-CaVβ function and ultimately be developed as a nonopioid therapeutic for chronic pain.
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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.