Evidence map›Paper›PMID 41946910›Full record

ReviewEMBO molecular medicine2026

Integrating chemical, genetic, and feasibility assessments for anti-tubercular target validation.

Dirk Schnappinger, Steven J Berthel, Helena I M Boshoff, Inna V Krieger, Paridhi Sukheja, Saswati Panda, Siddhant Rath, Kelsey Briggs, Xuelin Bian, Sari Rasheed and 13 more

Abstract readReview
In one paragraph

Review in EMBO molecular medicine, 2026. 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

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

23 authors.

Dirk SchnappingerDepartment of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, 10065, USA. dis2003@med.cornell.edu.ORCID 0000-0002-4445-7219
Steven J BerthelPanorama Global, Seattle, WA, USA.ORCID 0000-0003-1250-0208
Helena I M BoshoffTuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.ORCID 0000-0002-4333-206X
Inna V KriegerDepartment of Biochemistry and Biophysics, Texas A&M University, College Station, TX, USA.
Paridhi SukhejaCalibr-Skaggs Institute for Innovative Medicines, A Division of Scripps Research, La Jolla, CA, USA.
Saswati PandaDepartment of Biochemistry and Biophysics, Texas A&M University, College Station, TX, USA.ORCID 0000-0003-2057-8822
Siddhant RathDepartment of Biochemistry and Biophysics, Texas A&M University, College Station, TX, USA.ORCID 0000-0002-1179-0453
Kelsey BriggsGates Medical Research Institute, Cambridge, MA, USA.
Xuelin BianDepartment of Biochemistry and Biophysics, Texas A&M University, College Station, TX, USA.ORCID 0000-0002-5315-1203
Sari RasheedHelmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), PharmaScienceHub (PSH), Saarland University Campus, 66123, Saarbrücken, Germany.
Laura A T CleghornDrug Discovery Unit, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK.
Sandeep GhorpadeHolistic Drug Discovery and Development (H3D) Centre, Department of Chemistry, University of Cape Town, Rondebosch, 7701, South Africa.
Dirk A LamprechtHolistic Drug Discovery and Development (H3D) Centre, Department of Chemistry, University of Cape Town, Rondebosch, 7701, South Africa.
Nader FotouhiTB Alliance: Global Alliance for Tuberculosis Drug Development, New York, NY, USA.
Rolf MüllerHelmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), PharmaScienceHub (PSH), Saarland University Campus, 66123, Saarbrücken, Germany.ORCID 0000-0002-1042-5665
Carl NathanDepartment of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, 10065, USA.ORCID 0000-0002-7744-8896
Tanya ParishDepartment of Tropical Disease Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.
Kyu RheeDivision of Infectious Diseases, Weill Department of Medicine, Weill Cornell Medicine, New York, NY, 10021, USA.
Peter WarnerGates Foundation, Seattle, WA, USA.ORCID 0009-0006-9374-7024
Case W McNamaraCalibr-Skaggs Institute for Innovative Medicines, A Division of Scripps Research, La Jolla, CA, USA.
Jeremy M RockLaboratory of Host-Pathogen Biology, The Rockefeller University, New York, NY, 10065, USA.ORCID 0000-0002-9310-951X
James C SacchettiniDepartment of Biochemistry and Biophysics, Texas A&M University, College Station, TX, USA.
Valerie MizrahiMolecular Mycobacteriology Research Unit, Institute of Infectious Disease and Molecular Medicine & Department of Pathology, University of Cape Town, Cape Town, South Africa. Valerie.Mizrahi@uct.ac.za.ORCID 0000-0003-4824-9115

Funding

Bill and Melinda Gates Foundation (GF) INV-040484,INV-005757Bill and Melinda Gates Foundation (GF) INV-040487Bill and Melinda Gates Foundation (GF) INV-044686Bill and Melinda Gates Foundation (GF) INV-047552,INV-07007,INV-083642Bill and Melinda Gates Foundation (GF) INV-055896,INV-055894Bill and Melinda Gates Foundation (GF) INV-056399,INV-005585Bill and Melinda Gates Foundation (GF) INV-070003Gates Foundation INV-040482Global Alliance for TB Drug Development N/AHHS | National Institutes of Health (NIH) AI155510Milstein Program in Chemical Biology and Translational Medicine N/ASouth African Medical Research Council (SAMRC) N/A
6 · The paper itself

Abstract

Despite the approval of two first-in-class anti-tuberculars over the past two decades, the global burden of tuberculosis (TB) remains unacceptably high, in part due to the emergence and spread of drug-resistant strains of Mycobacterium tuberculosis (Mtb). This review summarizes advances and ongoing challenges in anti-TB drug discovery, focusing on identifying and validating novel targets. Highlighted is a framework developed by the TB Drug Accelerator (TBDA) consortium for target validation in Mtb. Two computational platforms, DAIKON and PARSNIP, allow the systematic evaluation of targets across multiple dimensions, including chemical validation, genetic essentiality, vulnerability, and the feasibility to identify drug-like molecules for a target of interest. Case studies of Pks13 and NadE illustrate how these parameters guide target prioritization and risk assessment. By integrating these metrics, the framework enables dynamic, transparent target ranking, supporting development of both pan-TB and treatment-shortening regimens. This paradigm is adaptable to other bacterial pathogens and is designed to improve evidence-based decision-making in antibacterial drug discovery.

Indexed as

Antitubercular AgentsDrug DiscoveryMycobacterium tuberculosisTuberculosisHumansAntitubercular AgentsAntibacterial Drug DevelopmentDatabaseTarget AssessmentTuberculosis

Identifiers

PMID41946910
PMCPMC13179349

What OpenQuestion holds

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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.