Evidence map›Paper›PMID 39868130›Full record

ArticlebioRxiv : the preprint server for biology2025

Docking 14 million virtual isoquinuclidines against the mu and kappa opioid receptors reveals dual antagonists-inverse agonists with reduced withdrawal effects.

Seth F Vigneron, Shohei Ohno, Joao Braz, Joseph Y Kim, Oh Sang Kweon, Chase Webb, Christian Billesbølle, Karnika Bhardwaj, John Irwin, Aashish Manglik and 3 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Seth F VigneronDepartment of Pharmaceutical Chemistry, University of California, San Francisco.ORCID 0000-0003-2671-3044
Shohei OhnoDepartment of Chemistry, Yale University.ORCID 0000-0002-2414-5066
Joao BrazDepartment of Anatomy, University of California, San Francisco.
Joseph Y KimDepartment of Pharmaceutical Chemistry, University of California, San Francisco.ORCID 0000-0002-6816-5958
Oh Sang KweonDepartment of Chemistry, Yale University.ORCID 0000-0001-6588-3420
Chase WebbDepartment of Pharmaceutical Chemistry, University of California, San Francisco.ORCID 0000-0003-2784-0408
Christian BillesbølleDepartment of Pharmaceutical Chemistry, University of California, San Francisco.ORCID 0000-0001-8084-1552
Karnika BhardwajDepartment of Anatomy, University of California, San Francisco.ORCID 0009-0000-1769-0210
John IrwinDepartment of Pharmaceutical Chemistry, University of California, San Francisco.ORCID 0000-0002-1195-6417
Aashish ManglikDepartment of Pharmaceutical Chemistry, University of California, San Francisco.ORCID 0000-0002-7173-3741
Allan I BasbaumDepartment of Anatomy, University of California, San Francisco.ORCID 0000-0002-1710-6333
Jonathan A EllmanDepartment of Chemistry, Yale University.ORCID 0000-0001-9320-5512
Brian K ShoichetDepartment of Pharmaceutical Chemistry, University of California, San Francisco.ORCID 0000-0002-6098-7367

Funding

Development and Testing of New Computational Methods for Ligand Discovery and MechanismR35GM122481 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Brian K Shoichet · 2017 to 2026
$8.5M
Next-generation C-H functionalization methods for organic synthesis and their applications to biological inquiryR35GM122473 · NIGMS · YALE UNIVERSITY · PI JONATHAN A ELLMAN · 2017 to 2026
$7.6M
From the spinal cord to the brain: Neurology of the pain and itch neuronsR35NS097306 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BASBAUM, ALLAN I. · 2017 to 2024
$7.2M
NIGMS NIH HHS R35 GM122473NIGMS NIH HHS R35 GM122481NINDS NIH HHS R35 NS097306
6 · The paper itself

Abstract

Large library docking of tangible molecules has revealed potent ligands across many targets. While make-on-demand libraries now exceed 75 billion enumerated molecules, their synthetic routes are dominated by a few reaction types, reducing diversity and inevitably leaving many interesting bioactive-like chemotypes unexplored. Here, we investigate the large-scale enumeration and targeted docking of isoquinuclidines. These "natural-product-like" molecules are rare in the current libraries and are functionally congested, making them interesting as receptor probes. Using a modular, four-component reaction scheme, we built and docked a virtual library of over 14.6 million isoquinuclidines against both the μ- and

Identifiers

PMID39868130
PMCPMC11760775

What OpenQuestion holds

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LicenceCC BY-ND
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Registered trials

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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.