Evidence map›Paper›PMID 38719475›Full record

ArticleMolecular pharmacology2024

Intracellular Allosteric Antagonist of the Olfactory Receptor OR51E2.

Tatjana Abaffy, Olivia Fu, Maira Harume-Nagai, Josh M Goldenberg, Victor Kenyon, Terry Kenakin

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Microbial volatile organic compounds and olfactory receptors in wound malodor.Frontiers in cellular and infection microbiology · 2026
    Pooled it
  2. Review
  3. Review
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Tatjana AbaffyDepartment of Molecular Genetics and Microbiology, School of Medicine, Duke University, Durham, North Carolina (T.A., O.F.); Columbia Center for Human Development/Columbia Center for Stem Cell Therapies Department, Columbia University, New York (M.H.-N.); Chemistry Department, School of Math and Science at the United States Naval Academy, Annapolis, Maryland (J.M.G.); Atomwise Inc., San Francisco, California (J.M.G., V.K.); and Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (T.K.) abaffyt@gmail.com.
Olivia FuDepartment of Molecular Genetics and Microbiology, School of Medicine, Duke University, Durham, North Carolina (T.A., O.F.); Columbia Center for Human Development/Columbia Center for Stem Cell Therapies Department, Columbia University, New York (M.H.-N.); Chemistry Department, School of Math and Science at the United States Naval Academy, Annapolis, Maryland (J.M.G.); Atomwise Inc., San Francisco, California (J.M.G., V.K.); and Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (T.K.).
Maira Harume-NagaiDepartment of Molecular Genetics and Microbiology, School of Medicine, Duke University, Durham, North Carolina (T.A., O.F.); Columbia Center for Human Development/Columbia Center for Stem Cell Therapies Department, Columbia University, New York (M.H.-N.); Chemistry Department, School of Math and Science at the United States Naval Academy, Annapolis, Maryland (J.M.G.); Atomwise Inc., San Francisco, California (J.M.G., V.K.); and Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (T.K.).
Josh M GoldenbergDepartment of Molecular Genetics and Microbiology, School of Medicine, Duke University, Durham, North Carolina (T.A., O.F.); Columbia Center for Human Development/Columbia Center for Stem Cell Therapies Department, Columbia University, New York (M.H.-N.); Chemistry Department, School of Math and Science at the United States Naval Academy, Annapolis, Maryland (J.M.G.); Atomwise Inc., San Francisco, California (J.M.G., V.K.); and Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (T.K.).
Victor KenyonDepartment of Molecular Genetics and Microbiology, School of Medicine, Duke University, Durham, North Carolina (T.A., O.F.); Columbia Center for Human Development/Columbia Center for Stem Cell Therapies Department, Columbia University, New York (M.H.-N.); Chemistry Department, School of Math and Science at the United States Naval Academy, Annapolis, Maryland (J.M.G.); Atomwise Inc., San Francisco, California (J.M.G., V.K.); and Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (T.K.).
Terry KenakinDepartment of Molecular Genetics and Microbiology, School of Medicine, Duke University, Durham, North Carolina (T.A., O.F.); Columbia Center for Human Development/Columbia Center for Stem Cell Therapies Department, Columbia University, New York (M.H.-N.); Chemistry Department, School of Math and Science at the United States Naval Academy, Annapolis, Maryland (J.M.G.); Atomwise Inc., San Francisco, California (J.M.G., V.K.); and Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (T.K.).

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Olfactory receptors are members of class A (rhodopsin-like) family of G protein-coupled receptors (GPCRs). Their expression and function have been increasingly studied in nonolfactory tissues, and many have been identified as potential therapeutic targets. In this manuscript, we focus on the discovery of novel ligands for the olfactory receptor family 51 subfamily E2 (OR51E2). We performed an artificial intelligence-based virtual drug screen of a ∼2.2 million small molecule library. Cell-based functional assay identified compound 80 (C80) as an antagonist and inverse agonist, and detailed pharmacological analysis revealed C80 acts as a negative allosteric modulator by significantly decreasing the agonist efficacy, while having a minimal effect on receptor affinity for agonist. C80 binds to an allosteric binding site formed by a network of nine residues localized in the intracellular parts of transmembrane domains 3, 5, 6, 7, and H8, which also partially overlaps with a G protein binding site. Mutational experiments of residues involved in C80 binding uncovered the significance of the C240

Indexed as

Allosteric SiteReceptors, OdorantAllosteric RegulationAnimalsBinding SitesCHO CellsCricetulusHEK293 CellsHumansLigandsSmall Molecule LibrariesLigandsReceptors, OdorantSmall Molecule Libraries

Identifiers

PMID38719475
PMCPMC11187688

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.