ArticleJournal of medicinal chemistry2014
Discovery of a potent and selective α3β4 nicotinic acetylcholine receptor antagonist from an α-conotoxin synthetic combinatorial library.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- The role of nicotinic receptors in alcohol consumption.Pharmacological research · 2023Pooled it
- From marine predator to pharmacology: Conotoxin diversity, discovery, and therapeutic potential.Zoological research · 2026Review
- What We Have Gained from Ibogaine: α3β4 Nicotinic Acetylcholine Receptor Inhibitors as Treatments for Substance Use Disorders.Journal of medicinal chemistry · 2023Review
- Fluorescently Labeled α-Conotoxin TxID, a New Probe for α3β4 Neuronal Nicotinic Acetylcholine Receptors.Marine drugs · 2022Article
- Mutagenesis of α-Conotoxins for Enhancing Activity and Selectivity for Nicotinic Acetylcholine Receptors.Toxins · 2019Review
- Neuronal Nicotinic Acetylcholine Receptor Modulators from Cone Snails.Marine drugs · 2018Review
- Differential regulation of alcohol taking and seeking by antagonism at α4β2 and α3β4 nAChRs.Psychopharmacology · 2018Article
- α-Conotoxins active at α3-containing nicotinic acetylcholine receptors and their molecular determinants for selective inhibition.British journal of pharmacology · 2018Review
- α-Conotoxin [S9A]TxID Potently Discriminates between α3β4 and α6/α3β4 Nicotinic Acetylcholine Receptors.Journal of medicinal chemistry · 2017Article
- Structural mechanisms for α-conotoxin activity at the human α3β4 nicotinic acetylcholine receptor.Scientific reports · 2017Article
- Direct Phenotypic Screening in Mice: Identification of Individual, Novel Antinociceptive Compounds from a Library of 734,821 Pyrrolidine Bis-piperazines.ACS combinatorial science · 2016Article
- Review
- Alanine scan of α-conotoxin RegIIA reveals a selective α3β4 nicotinic acetylcholine receptor antagonist.The Journal of biological chemistry · 2015Article
- Mixture-based combinatorial libraries from small individual peptide libraries: a case study on α1-antitrypsin deficiency.Molecules (Basel, Switzerland) · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
α-Conotoxins are disulfide-rich peptide neurotoxins that selectively inhibit neuronal nicotinic acetylcholine receptors (nAChRs). The α3β4 nAChR subtype has been identified as a novel target for managing nicotine addiction. Using a mixture-based positional-scanning synthetic combinatorial library (PS-SCL) with the α4/4-conotoxin BuIA framework, we discovered a highly potent and selective α3β4 nAChR antagonist. The initial PS-SCL consisted of a total of 113 379 904 sequences that were screened for α3β4 nAChR inhibition, which facilitated the design and synthesis of a second generation library of 64 individual α-conotoxin derivatives. Eleven analogues were identified as α3β4 nAChR antagonists, with TP-2212-59 exhibiting the most potent antagonistic activity and selectivity over the α3β2 and α4β2 nAChR subtypes. Final electrophysiological characterization demonstrated that TP-2212-59 inhibited acetylcholine evoked currents in α3β4 nAChRs heterogeneously expressed in Xenopus laevis oocytes with a calculated IC50 of 2.3 nM and exhibited more than 1000-fold selectivity over the α3β2 and α7 nAChR subtypes. As such, TP-2212-59 is among the most potent α3β4 nAChRs antagonists identified to date and further demonstrates the utility of mixture-based combinatorial libraries in the discovery of novel α-conotoxin derivatives with refined pharmacological activity.
Indexed as
Identifiers
What OpenQuestion holds
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.