ArticleThe Journal of clinical investigation2014
Conjugation of a brain-penetrant peptide with neurotensin provides antinociceptive properties.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
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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.
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Who cites it
47 citing papers in PubMed, 109 citations in OpenAlex.
- Article
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- Identification of Variable Lymphocyte Receptors That Target the Human Blood-Brain Barrier.Pharmaceutics · 2025Article
- Influence of the neurotensin signaling system on feeding and satiety.Neuropharmacology · 2025Review
- Article
- Impact of Peptide Transport and Memory Function in the Brain.Nutrients · 2024Review
- Receptor-mediated transcytosis for brain delivery of therapeutics: receptor classes and criteria.Frontiers in drug delivery · 2024Review
- Peptide-Based Agents for Cancer Treatment: Current Applications and Future Directions.International journal of molecular sciences · 2023Review
- Peptides for trans-blood-brain barrier delivery.Journal of labelled compounds & radiopharmaceuticals · 2023Review
- Review
- CDR3 Variants of the TXB2 Shuttle with Increased TfR1 Association Rate and Enhanced Brain Penetration.Pharmaceutics · 2023Article
- Influence of the Drug Position on Bioactivity in Angiopep-2-Daunomycin Conjugates.International journal of molecular sciences · 2023Article
- Peptides as Pharmacological Carriers to the Brain: Promises, Shortcomings and Challenges.Molecular pharmaceutics · 2022Review
- Peptide Shuttles for Blood-Brain Barrier Drug Delivery.Pharmaceutics · 2022Review
- The 46.1 Antibody Mediates Neurotensin Uptake into the CNS and the Effects Depend on the Route of Intravenous Administration.Pharmaceutics · 2022Article
- Neurophysiological mechanisms of cancer-induced bone pain.Journal of advanced research · 2022Review
- Biological Membrane-Penetrating Peptides: Computational Prediction and Applications.Frontiers in cellular and infection microbiology · 2022Review
- Low-Level Endothelial TRAIL-Receptor Expression Obstructs the CNS-Delivery of Angiopep-2 Functionalised TRAIL-Receptor Agonists for the Treatment of Glioblastoma.Molecules (Basel, Switzerland) · 2021Article
- Development of Novel Therapeutics Targeting the Blood-Brain Barrier: From Barrier to Carrier.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
Abstract
Neurotensin (NT) has emerged as an important modulator of nociceptive transmission and exerts its biological effects through interactions with 2 distinct GPCRs, NTS1 and NTS2. NT provides strong analgesia when administered directly into the brain; however, the blood-brain barrier (BBB) is a major obstacle for effective delivery of potential analgesics to the brain. To overcome this challenge, we synthesized chemical conjugates that are transported across the BBB via receptor-mediated transcytosis using the brain-penetrant peptide Angiopep-2 (An2), which targets LDL receptor-related protein-1 (LRP1). Using in situ brain perfusion in mice, we found that the compound ANG2002, a conjugate of An2 and NT, was transported at least 10 times more efficiently across the BBB than native NT. In vitro, ANG2002 bound NTS1 and NTS2 receptors and maintained NT-associated biological activity. In rats, i.v. ANG2002 induced a dose-dependent analgesia in the formalin model of persistent pain. At a dose of 0.05 mg/kg, ANG2002 effectively reversed pain behaviors induced by the development of neuropathic and bone cancer pain in animal models. The analgesic properties of ANG2002 demonstrated in this study suggest that this compound is effective for clinical management of persistent and chronic pain and establish the benefits of this technology for the development of neurotherapeutics.
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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.