ArticleProceedings of the National Academy of Sciences of the United States of America2021
Identification of tetracycline combinations as EphB1 tyrosine kinase inhibitors for treatment of neuropathic pain.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Targeting druggable kinases in neuropathic pain.npj drug discovery · 2026Review
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- Peripheral neuronal sensitization and neurovascular remodelling in osteoarthritis pain.Nature reviews. Rheumatology · 2025Review
- Ectopic Nociceptor Sprouting as a Key Peripheral Driver of Pain in Rheumatoid Arthritis.Current rheumatology reports · 2025Review
- Methods for Controlling Small GTPase Activity.Chembiochem : a European journal of chemical biology · 2025Review
- An FDA-approved drug structurally and phenotypically corrects the K210del mutation in genetic cardiomyopathy models.The Journal of clinical investigation · 2025Article
- Drug repurposing of argatroban, glimepiride and ranolazine shows anti-SARS-CoV-2 activity via diverse mechanisms.Heliyon · 2025Article
- Advances in Drug Discovery for Cardiomyocyte Proliferation.Current treatment options in cardiovascular medicine · 2025Review
- Article
- ephrin-B2 promotes nociceptive plasticity and hyperalgesic priming through EphB2-MNK-eIF4E signaling in both mice and humans.Pharmacological research · 2024Article
- Ephs in cancer progression: complexity and context-dependent nature in signaling, angiogenesis and immunity.Cell communication and signaling : CCS · 2024Review
- Identification of FDA-approved drugs that induce heart regeneration in mammals.Nature cardiovascular research · 2024Article
- Antimicrobial therapies for chronic pain (part 2): the prevention and treatment of chronic pain.The Korean journal of pain · 2023Review
- FDA approved drugs with antiviral activity against SARS-CoV-2: From structure-based repurposing to host-specific mechanisms.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Article
- Review
- Hit Identification of a Novel Quinazoline Sulfonamide as a Promising EphB3 Inhibitor: Design, Virtual Combinatorial Library, Synthesis, Biological Evaluation, and Docking Simulation Studies.Pharmaceuticals (Basel, Switzerland) · 2021Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Previous studies have demonstrated that the synaptic EphB1 receptor tyrosine kinase is a major mediator of neuropathic pain, suggesting that targeting the activity of this receptor might be a viable therapeutic option. Therefore, we set out to determine if any FDA-approved drugs can act as inhibitors of the EphB1 intracellular catalytic domain. An in silico screen was first used to identify a number of tetracycline antibiotics which demonstrated potential docking to the ATP-binding catalytic domain of EphB1. Kinase assays showed that demeclocycline, chlortetracycline, and minocycline inhibit EphB1 kinase activity at low micromolar concentrations. In addition, we cocrystallized chlortetracycline and EphB1 receptor, which confirmed its binding to the ATP-binding domain. Finally, in vivo administration of the three-tetracycline combination inhibited the phosphorylation of EphB1 in the brain, spinal cord, and dorsal root ganglion (DRG) and effectively blocked neuropathic pain in mice. These results indicate that demeclocycline, chlortetracycline, and minocycline can be repurposed for treatment of neuropathic pain and potentially for other indications that would benefit from inhibition of EphB1 receptor kinase activity.
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