ArticleScience translational medicine2021
Selective targeting of NaV1.7 via inhibition of the CRMP2-Ubc9 interaction reduces pain in rodents.
Article in Science translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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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.
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Who cites it
33 citing papers in PubMed, 53 citations in OpenAlex.
- Spared but Not Silent: Ion Channel Plasticity in Uninjured Sensory Neurons in Neuropathic Pain.International journal of molecular sciences · 2026Review
- NabioRxiv : the preprint server for biology · 2026Article
- Human α1-Antitrypsin Inhibits Nociceptor Excitability and Relieves Inflammatory and Neuropathic Pain.Biomolecules · 2026Article
- Targeting CRMP2 for Chronic Pain: From Molecular Mechanisms to Therapeutic Strategies.Biomedicines · 2026Review
- Epigenetic mechanisms of HIV and opioid-induced neuropathology: Potential therapies and interventions.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- BH4 Oxidation-Derived HJournal of neurochemistry · 2025Article
- Beyond single targets: leveraging degeneracy in sodium channels for osteoarthritis analgesia.Pain reports · 2025Article
- Ion channels as therapeutic targets in osteoarthritis.Trends in pharmacological sciences · 2025Review
- Sensory neuron-expressed FGF13 controls nociceptive signaling in diabetic neuropathy models.The Journal of clinical investigation · 2025Article
- Sculpting excitable membranes: voltage-gated ion channel delivery and distribution.Nature reviews. Neuroscience · 2025Review
- Voltage-gated sodium channels in excitable cells as drug targets.Nature reviews. Drug discovery · 2025Review
- Preclinical Animal Models to Investigate the Role of NaLife (Basel, Switzerland) · 2025Review
- Synergistic Inhibition of Nav1.7 and NCX1: A Novel Strategy for Treating Cancer-Induced Bone Pain by Modulating Pain Sensitization and Neuronal Inflammation.CNS neuroscience & therapeutics · 2025Article
- SUMOylation and DeSUMOylation: Tug of War of Pain Signaling.Molecular neurobiology · 2025Review
- Small-molecule natural product sophoricoside reduces peripheral neuropathic pain via directly blocking of NaV1.6 in dorsal root ganglion nociceptive neurons.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Discordance between preclinical and clinical testing of Na V 1.7-selective inhibitors for pain.Pain · 2025Review
- Article
- 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
- Discovery of Loureirin analogues with colorectal cancer suppressive activity via regulating cell cycle and Fas death receptor.BMC pharmacology & toxicology · 2024Article
- Regulating neuronal excitability: The role ofPNAS nexus · 2024Article
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Authors and funding
25 authors at 5 institutions in 2 countries.
Funding
Abstract
The voltage-gated sodium NaV1.7 channel, critical for sensing pain, has been actively targeted by drug developers; however, there are currently no effective and safe therapies targeting NaV1.7. Here, we tested whether a different approach, indirect NaV1.7 regulation, could have antinociceptive effects in preclinical models. We found that preventing addition of small ubiquitin-like modifier (SUMO) on the NaV1.7-interacting cytosolic collapsin response mediator protein 2 (CRMP2) blocked NaV1.7 functions and had antinociceptive effects in rodents. In silico targeting of the SUMOylation site in CRMP2 (Lys374) identified >200 hits, of which compound 194 exhibited selective in vitro and ex vivo NaV1.7 engagement. Orally administered 194 was not only antinociceptive in preclinical models of acute and chronic pain but also demonstrated synergy alongside other analgesics—without eliciting addiction, rewarding properties, or neurotoxicity. Analgesia conferred by 194 was opioid receptor dependent. Our results demonstrate that 194 is a first-in-class protein-protein inhibitor that capitalizes on CRMP2-NaV1.7 regulation to deliver safe analgesia in rodents.
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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.