Evidence map›Paper›PMID 39468773›Full record

ArticleJournal of medicinal chemistry2024

Rational Exploration of 2,4-Diaminopyrimidines as DHFR Inhibitors Active against

Matheus Andrade Meirelles, Vitor M Almeida, Jaryd R Sullivan, Ian de Toledo, Caio Vinicius Dos Reis, Micael Rodrigues Cunha, Rachel Zigweid, Abraham Shim, Banumathi Sankaran, Elijah L Woodward and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of medicinal chemistry, 2024. 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. 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

25 authors.

Matheus Andrade MeirellesDepartment of Organic Chemistry, Institute of Chemistry, University of Campinas, UNICAMP, 13083-970-Campinas, SP, Brazil.ORCID 0000-0002-2097-4270
Vitor M AlmeidaCenter of Medicinal Chemistry (CQMED), Center for Molecular Biology and Genetic Engineering (CBMEG), University of Campinas, UNICAMP, 13083-886-Campinas, SP, Brazil.
Jaryd R SullivanDepartment of Microbiology & Immunology, McGill University, Montréal H3A 2B4, Canada.
Ian de ToledoDepartment of Organic Chemistry, Institute of Chemistry, University of Campinas, UNICAMP, 13083-970-Campinas, SP, Brazil.
Caio Vinicius Dos ReisCenter of Medicinal Chemistry (CQMED), Center for Molecular Biology and Genetic Engineering (CBMEG), University of Campinas, UNICAMP, 13083-886-Campinas, SP, Brazil.
Micael Rodrigues CunhaCenter of Medicinal Chemistry (CQMED), Center for Molecular Biology and Genetic Engineering (CBMEG), University of Campinas, UNICAMP, 13083-886-Campinas, SP, Brazil.ORCID 0000-0001-5227-6816
Rachel ZigweidCenter for Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington 98109, United States.
Abraham ShimCenter for Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington 98109, United States.
Banumathi SankaranMolecular Biophysics and Integrated Bioimaging, Berkeley Center for Structural Biology, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States.
Elijah L WoodwardSeattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, Washington 98109, United States.
Steve SeiboldSeattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, Washington 98109, United States.
Lijun LiuSeattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, Washington 98109, United States.
Mohammad Rasel MianSeattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, Washington 98109, United States.
Kevin P BattaileNew York Structural Biology Center, Upton, New York 11973, United States.
Jennifer RileyDrug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry, University of Dundee, Dundee DD1 5EH, U.K.
Christina DuncanDrug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry, University of Dundee, Dundee DD1 5EH, U.K.
Frederick R C SimeonsDrug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry, University of Dundee, Dundee DD1 5EH, U.K.
Liam FergusonDrug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry, University of Dundee, Dundee DD1 5EH, U.K.
Halimatu JojiDrug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry, University of Dundee, Dundee DD1 5EH, U.K.
Kevin D ReadDrug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry, University of Dundee, Dundee DD1 5EH, U.K.ORCID 0000-0002-8536-0130
Scott LovellSeattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, Washington 98109, United States.
Bart L StakerCenter for Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington 98109, United States.ORCID 0000-0001-9570-5086
Marcel A BehrDepartment of Microbiology & Immunology, McGill University, Montréal H3A 2B4, Canada.
Ronaldo A PilliDepartment of Organic Chemistry, Institute of Chemistry, University of Campinas, UNICAMP, 13083-970-Campinas, SP, Brazil.
Rafael M CouñagoCenter of Medicinal Chemistry (CQMED), Center for Molecular Biology and Genetic Engineering (CBMEG), University of Campinas, UNICAMP, 13083-886-Campinas, SP, Brazil.ORCID 0000-0003-1847-5090

Funding

User Training and OutreachP30GM124169 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI PAUL David ADAMS, Gregory L Hura · 2017 to 2026
$28.6M
Centers for Research on Structural Biology of Infectious Diseases: Universal Influenza Vaccine Research75N93022C00036 · NIAID · SEATTLE CHILDREN'S HOSPITAL · PI STAKER, BART · 2022 to 2025
$21.7M
An Eiger2 XE 9M detector for the NYSBC-operated NYX beamline at NSLS-IIS10OD030394 · OD · NEW YORK STRUCTURAL BIOLOGY CENTER · PI BATTAILE, KEVIN P · 2021 to 2021
$1.8M
NIAID NIH HHS 75N93022C00036NIAID NIH HHS HHSN272200700057CNIAID NIH HHS HHSN272201200025CNIAID NIH HHS HHSN272201700059CNIGMS NIH HHS P30 GM124169NIH HHS S10 OD030394Wellcome Trust
6 · The paper itself

Abstract

Nontuberculous mycobacteria (NTM) are emerging human pathogens linked to severe pulmonary diseases. Current treatments involve the prolonged use of multiple drugs and are often ineffective. Bacterial dihydrofolate reductase (DHFR) is a key enzyme targeted by antibiotics in Gram-negative bacterial infections. However, existing DHFR inhibitors designed for Gram-negative bacteria often fail against mycobacterial DHFRs. Here, we detail the rational design of NTM DHFR inhibitors based on

Indexed as

Folic Acid AntagonistsMycobacterium abscessusMycobacterium aviumPyrimidinesTetrahydrofolate DehydrogenaseAnti-Bacterial AgentsHumansMicrobial Sensitivity TestsStructure-Activity Relationship2,4-diaminopyrimidineAnti-Bacterial AgentsFolic Acid AntagonistsPyrimidinesTetrahydrofolate Dehydrogenase

Identifiers

PMID39468773
PMCPMC12286596

What OpenQuestion holds

Textmetadata
LicenceTDM
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.