ArticleJournal of medicinal chemistry2011
Discovery of a potent and efficacious peptide derivative for δ/μ opioid agonist/neurokinin 1 antagonist activity with a 2',6'-dimethyl-L-tyrosine: in vitro, in vivo, and NMR-based structural studies.
Article in Journal of medicinal chemistry, 2011. 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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Who cites it
15 citing papers in PubMed, 30 citations in OpenAlex.
- Rational Design of Putative Dual-Target Opioid-Dopaminergic Casomorphin-Ranatensin Hybrid Peptides: Computational Modeling and Preliminary Antiproliferative Evaluation.Molecules (Basel, Switzerland) · 2026Article
- Novel Mixed NOP/Opioid Receptor Peptide Agonists.Journal of medicinal chemistry · 2021Article
- Synthesis and Pharmacological Evaluation of Hybrids Targeting Opioid and Neurokinin Receptors.Molecules (Basel, Switzerland) · 2019Article
- Genetic and pharmacological antagonism of NKMolecular psychiatry · 2018Article
- Novel Pharmacological Nonopioid Therapies in Chronic Pain.Current pain and headache reports · 2018Review
- Novel Molecular Strategies and Targets for Opioid Drug Discovery for the Treatment of Chronic Pain.The Yale journal of biology and medicine · 2017Review
- Neurokinin 1 and opioid receptors: relationships and interactions in nervous system.Translational perioperative and pain medicine · 2016Article
- Dual Alleviation of Acute and Neuropathic Pain by Fused Opioid Agonist-Neurokinin 1 Antagonist Peptidomimetics.ACS medicinal chemistry letters · 2015Article
- Discovery of Novel Multifunctional Ligands with μ/δ Opioid Agonist/Neurokinin-1 (NK1) Antagonist Activities for the Treatment of Pain.Journal of medicinal chemistry · 2015Article
- Discovery of tripeptide-derived multifunctional ligands possessing delta/mu opioid receptor agonist and neurokinin 1 receptor antagonist activities.Bioorganic & medicinal chemistry letters · 2015Article
- Investigational peptide and peptidomimetic μ and δ opioid receptor agonists in the relief of pain.Expert opinion on investigational drugs · 2014Review
- Novel fentanyl-based dual μ/δ-opioid agonists for the treatment of acute and chronic pain.Life sciences · 2013Article
- Truncation of the peptide sequence in bifunctional ligands with mu and delta opioid receptor agonist and neurokinin 1 receptor antagonist activities.Bioorganic & medicinal chemistry letters · 2013Article
- Biological active analogues of the opioid peptide biphalin: mixed α/β(3)-peptides.Journal of medicinal chemistry · 2013Article
- In vivo antinociception of potent mu opioid agonist tetrapeptide analogues and comparison with a compact opioid agonist-neurokinin 1 receptor antagonist chimera.Molecular brain · 2012Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Multivalent ligands with δ/μ opioid agonist and NK1 antagonist activities have shown promising analgesic potency without detectable sign of toxicities, including motor skill impairment and opioid-induced tolerance. To improve their biological activities and metabolic stability, structural optimization was performed on our peptide-derived lead compounds by introducing 2',6'-dimethyl-L-tyrosine (Dmt) instead of Tyr at the first position. The compound 7 (Dmt-D-Ala-Gly-Phe-Met-Pro-Leu-Trp-NH-[3',5'-(CF(3))(2)-Bzl]) showed improved multivalent bioactivities compared to those of the lead compounds, had more than 6 h half-life in rat plasma, and had significant antinociceptive efficacy in vivo. The NMR structural analysis suggested that Dmt(1) incorporation in compound 7 induces the structured conformation in the opioid pharmacophore (N-terminus) and simultaneously shifts the orientation of the NK1 pharmacophore (C-terminus), consistent with its affinities and activities at both opioid and NK1 receptors. These results indicate that compound 7 is a valuable research tool to seek a novel analgesic drug.
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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.