Evidence map›Paper›PMID 42428492›Full record

ArticleFrontiers in pharmacology2026

Structure-based virtual screening for selective connexin hemichannel blockers: a historical perspective on the discovery of a small organic inhibitor.

Carlos F Lagos, Anibal Vargas, Anibal García, Yorley Duarte, Chenju Yi, Juan C Sáez

Abstract read
In one paragraph

Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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.

Carlos F LagosChemical Biology and Drug Discovery Lab, Escuela de Química y Farmacia, Facultad de Ciencias, Universidad San Sebastián, Santiago, Chile.
Anibal VargasCenter of Integrative Biology, Faculty of Science, Universidad Mayor, Santiago, Chile.
Anibal GarcíaInstituto de Neurociencias, Centro Interdisciplinario de Neurociencias de Valparaíso, Universidad de Valparaíso, Valparaíso, Chile.
Yorley DuarteCenter for Bioinformatics and Integrative Biology, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, Chile.
Chenju YiDepartment of Geriatrics, Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.
Juan C SáezInstituto de Neurociencias, Centro Interdisciplinario de Neurociencias de Valparaíso, Universidad de Valparaíso, Valparaíso, Chile.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Connexin hemichannels are critical mediators of cellular signaling in both physiological and pathological states, yet their selective pharmacological modulation has remained elusive because of the close structural similarity between hemichannels and gap junction channels formed by the same connexins. Methods: We combined structure-based virtual screening of a connexin hemichannel model with experimental validation - ethidium/DAPI dye-uptake assays, single-channel and whole-cell electrophysiology, and Lucifer yellow gap-junctional coupling assays - to identify and characterise D4, a small chiral organic molecule, and we synthesised and tested both of its enantiomers. Results: D4(R) potently and selectively blocks C×43 hemichannels at nanomolar concentrations (IC Discussion: These findings establish D4(R) as a first-in-class, gap-junction-sparing hemichannel blocker and provide a validated molecular scaffold for next-generation connexin therapeutics, addressing a long-standing challenge in connexin pharmacology and opening new avenues for dissecting hemichannel function under physiological and pathophysiological conditions.

Indexed as

connexinD4gap junctionhemichannelselective blockerstructure-based drug designvirtual screening

Identifiers

PMID42428492
PMCPMC13345830

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.