ArticleJournal of medicinal chemistry2013
Scaffold ranking and positional scanning utilized in the discovery of nAChR-selective compounds suitable for optimization studies.
Article in Journal of medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Novel Lipophagy Inducers as Potential Therapeutics for Lipid Metabolism Disorders.ACS chemical biology · 2025Article
- Selective Signal Capture from Multidimensional GPCR Outputs with Biased Agonists: Progress Towards Novel Drug Development.Molecular diagnosis & therapy · 2022Review
- 1,5-Disubstituted Acylated 2-Amino-4,5-dihydroimidazoles as a New Class of Retinoic Acid Receptor-Related Orphan Receptor (ROR) Inhibitors.International journal of molecular sciences · 2022Article
- Biased β-Agonists Favoring Gs over β-Arrestin for Individualized Treatment of Obstructive Lung Disease.Journal of personalized medicine · 2022Review
- Malaria Parasite Plasmodium falciparum Proteins on the Surface of Infected Erythrocytes as Targets for Novel Drug Discovery.Biochemistry. Biokhimiia · 2022Review
- Identification and characterization of an atypical Gαs-biased βProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Small Molecule Compounds Identified from Mixture-Based Library Inhibit Binding betweenInternational journal of molecular sciences · 2021Article
- Discovery of a Lead Compound for Specific Inhibition of Type I Collagen Production in Fibrosis.ACS medicinal chemistry letters · 2021Article
- Type IA Topoisomerases as Targets for Infectious Disease Treatments.Microorganisms · 2021Review
- Scaffold Ranking and Positional Scanning Identify Novel Neurite Outgrowth Promoters with Nanomolar Potency.ACS medicinal chemistry letters · 2018Article
- Differential regulation of alcohol taking and seeking by antagonism at α4β2 and α3β4 nAChRs.Psychopharmacology · 2018Article
- Identification of a small molecule inhibitor of the aminoglycoside 6'-N-acetyltransferase type Ib [AAC(6')-Ib] using mixture-based combinatorial libraries.International journal of antimicrobial agents · 2018Article
- Identification of a Novel Polyamine Scaffold With Potent Efflux Pump Inhibition Activity Toward Multi-Drug Resistant Bacterial Pathogens.Frontiers in microbiology · 2018Article
- Highly Selective and Potent α4β2 nAChR Antagonist Inhibits Nicotine Self-Administration and Reinstatement in Rats.Journal of medicinal chemistry · 2017Article
- Identification of a Hit Series of Antileishmanial Compounds through the Use of Mixture-Based Libraries.ACS medicinal chemistry letters · 2017Article
- Small-Molecule Inhibitors Targeting Topoisomerase I as Novel Antituberculosis Agents.Antimicrobial agents and chemotherapy · 2016Article
- Direct Phenotypic Screening in Mice: Identification of Individual, Novel Antinociceptive Compounds from a Library of 734,821 Pyrrolidine Bis-piperazines.ACS combinatorial science · 2016Article
- Identification of Protein Palmitoylation Inhibitors from a Scaffold Ranking Library.Combinatorial chemistry & high throughput screening · 2016Article
- Identification of Small Molecule Inhibitors of Human As(III) S-Adenosylmethionine Methyltransferase (AS3MT).Chemical research in toxicology · 2015Article
- Combinatorial Libraries As a Tool for the Discovery of Novel, Broad-Spectrum Antibacterial Agents Targeting the ESKAPE Pathogens.Journal of medicinal chemistry · 2015Article
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Authors and funding
11 authors.
Funding
Abstract
Nicotine binds to nicotinic acetylcholine receptors (nAChR), which can exist as many different subtypes. The α4β2 nAChR is the most prevalent subtype in the brain and possesses the most evidence linking it to nicotine seeking behavior. Herein we report the use of mixture based combinatorial libraries for the rapid discovery of a series of α4β2 nAChR selective compounds. Further chemistry optimization provided compound 301, which was characterized as a selective α4β2 nAChR antagonist. This compound displayed no agonist activity but blocked nicotine-induced depolarization of HEK cells with an IC50 of approximately 430 nM. 301 demonstrated nearly 500-fold selectivity for binding and 40-fold functional selectivity for α4β2 over α3β4 nAChR. In total over 5 million compounds were assessed through the use of just 170 samples in order to identify a series of structural analogues suitable for future optimization toward the goal of developing clinically relevant smoking cessation medications.
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