ArticleEBioMedicine2020
SP6616 as a Kv2.1 inhibitor efficiently ameliorates peripheral neuropathy in diabetic mice.
Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 33 citations in OpenAlex.
- Selective inhibition of monoamine oxidase B represents a therapeutic strategy for diabetic peripheral neuropathy.Acta pharmacologica Sinica · 2026Article
- Otilonium bromide ameliorates paclitaxel-induced peripheral neuropathy by targeting phosphatase PPM1A.Journal of neuroinflammation · 2026Article
- High glucose mediates diabetic peripheral neuropathy by inducing Schwann cells apoptosis through the Dgkh/PKC-α signaling pathway.Acta diabetologica · 2025Article
- Desloratadine as the selective 5HTJournal of neuroinflammation · 2025Article
- Glabridin as a selective Kv2.1 inhibitor ameliorates DPN pathology by disrupting the Aβ/Kv2.1/JNK/NF-κB/NLRP3/p-Tau pathway.Acta pharmacologica Sinica · 2025Article
- Drofenine as a Kv2.1 inhibitor alleviated AD-like pathology in mice through AActa pharmaceutica Sinica. B · 2025Article
- Desloratadine ameliorates paclitaxel-induced peripheral neuropathy and hypersensitivity reactions in mice.Acta pharmacologica Sinica · 2024Article
- Targeted metabolomics reveals the aberrant energy status in diabetic peripheral neuropathy and the neuroprotective mechanism of traditional Chinese medicine JinMaiTong.Journal of pharmaceutical analysis · 2024Article
- Characterization of sensory and motor dysfunction and morphological alterations in late stages of type 2 diabetic mice.Frontiers in endocrinology · 2024Article
- Vincamine as an agonist of G-protein-coupled receptor 40 effectively ameliorates diabetic peripheral neuropathy in mice.Acta pharmacologica Sinica · 2023Article
- Article
- Neuron-Schwann cell interactions in peripheral nervous system homeostasis, disease, and preclinical treatment.Frontiers in cellular neuroscience · 2023Review
- FX5, a non-steroidal glucocorticoid receptor antagonist, ameliorates diabetic cognitive impairment in mice.Acta pharmacologica Sinica · 2022Article
- The role of voltage-gated ion channels in visual function and disease in mammalian photoreceptors.Pflugers Archiv : European journal of physiology · 2021Review
- Roles of AMPK and Its Downstream Signals in Pain Regulation.Life (Basel, Switzerland) · 2021Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDiabetic peripheral neuropathy (DPN) is a common complication of diabetes severely afflicting the patients, while there is yet no effective medication against this disease. As Kv2.1 channel functions potently in regulating neurological disorders, the present work was to investigate the regulation of Kv2.1 channel against DPN-like pathology of DPN model mice by using selective Kv2.1 inhibitor SP6616 (ethyl 5-(3-ethoxy-4-methoxyphenyl)-2-(4-hydroxy-3-methoxybenzylidene)-7-methyl-3-oxo-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylate) as a probe.
methodsSTZ-induced type 1 diabetic mice with DPN (STZ mice) were defined at 12 weeks of age (4 weeks after STZ injection) through behavioral tests, and db/db (BKS Cg-m
findingsSP6616 treatment effectively ameliorated the threshold of mechanical stimuli, thermal sensitivity and MNCV of diabetic mice. Mechanism research results indicated that SP6616 suppressed Kv2.1 expression, increased the number of intraepidermal nerve fibers (IENFs), improved peripheral nerve structure and vascular function in DRG tissue. In addition, SP6616 improved mitochondrial dysfunction through Kv2.1/CaMKKβ/AMPK/PGC-1α pathway, repressed inflammatory response by inhibiting Kv2.1/NF-κB signaling and alleviated apoptosis of DRG neuron through Kv2.1-mediated regulation of Bcl-2 family proteins and Caspase-3 in diabetic mice.
interpretationOur work has highly supported the beneficial of Kv2.1 inhibition in ameliorating DPN-like pathology and highlighted the potential of SP6616 in the treatment of DPN.
fundingPlease see funding sources.
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