Evidence map›Paper›PMID 36190786›Full record

ArticleJournal of computational chemistry2022

Toward more potent imidazopyridine inhibitors of Candida albicans Bdf1: Modeling the role of structural waters in selective ligand binding.

Yingsheng Zhou, Justin M Overhulse, Nathan J Dupper, Yanchun Guo, Boris A Kashemirov, Kaiyao Wei, Jérôme Govin, Carlo Petosa, Charles E McKenna

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of computational chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.5field-weighted citation impact, top 33% of its field
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

2 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
  2. Article
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

9 authors at 2 institutions in 2 countries.

Yingsheng ZhouDepartment of Chemistry, University of Southern California, Los Angeles, California, USA.
Justin M OverhulseDepartment of Chemistry, University of Southern California, Los Angeles, California, USA.
Nathan J DupperDepartment of Chemistry, University of Southern California, Los Angeles, California, USA.
Yanchun GuoDepartment of Chemistry, University of Southern California, Los Angeles, California, USA.
Boris A KashemirovDepartment of Chemistry, University of Southern California, Los Angeles, California, USA.
Kaiyao WeiUniv. Grenoble Alpes, CEA, CNRS, Institut de Biologie Structurale (IBS), Grenoble, 38000, France.
Jérôme GovinUniv. Grenoble Alpes, Inserm, CNRS, Institute for Advanced Biosciences (IAB), Grenoble, 38000, France.ORCID 0000-0001-5511-6965
Carlo PetosaUniv. Grenoble Alpes, CEA, CNRS, Institut de Biologie Structurale (IBS), Grenoble, 38000, France.ORCID 0000-0002-9975-1167
Charles E McKennaDepartment of Chemistry, University of Southern California, Los Angeles, California, USA.ORCID 0000-0002-3540-6663
University of Southern California · USCentre National de la Recherche Scientifique · FR

Funding

CBI: Chemistry Biology InterfaceT32GM118289 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI FORSBURG, SUSAN L · 2016 to 2020
$1.2M
Selective inhibition of fungal BET protein Bdf1R21AI113704 · NIAID · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MCKENNA, CHARLES E · 2016 to 2017
$454k
ANR ANR-18-CE18-0007CEA PhD fellowshipFinovi FoundationFondation Innovations en InfectiologieNIAID NIH HHS R21 AI113704NIGMS NIH HHS T32 GM118289NIH HHS T32 GM118289USC Bridge Institute
6 · The paper itself

Abstract

Novel agents to treat invasive fungal infections are urgently needed because the small number of established targets in pathogenic fungi makes the existing drug repertoire particularly vulnerable to the emergence of resistant strains. Recently, we reported that Candida albicans Bdf1, a bromodomain and extra-terminal domain (BET) bromodomain with paired acetyl-lysine (AcK) binding sites (BD1 and BD2) is essential for fungal cell growth and that an imidazopyridine (1) binds to BD2 with selectivity versus both BD1 and human BET bromodomains. Bromodomain binding pockets contain a conserved array of structural waters. Molecular dynamics simulations now reveal that one water molecule is less tightly bound to BD2 than to BD1, explaining the site selectivity of 1. This insight is useful in the performance of ligand docking studies to guide design of more effective Bdf1 inhibitors, as illustrated by the design of 10 new imidazopyridine BD2 ligands 1a-j, for which experimental binding and site selectivity data are presented.

Indexed as

Candida albicansTranscription FactorsBinding SitesHumansImidazolesLigandsPyridinesImidazolesimidazopyridineLigandsPyridinesTranscription Factorsantifungal drugsBET inhibitionbromodomainsCandida albicansmolecular dynamicsreceptor-binding modelstructural water

Identifiers

PMID36190786
PMCPMC9669269
OpenAlexW4300690188

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.