Evidence map›Paper›PMID 41530381›Full record

ArticleNature medicine2026

Discovery and development of a new oxazolidinone with reduced toxicity for the treatment of tuberculosis.

Brendan M Crowley, Helena I Boshoff, Aidan Boving, Vee Y Tan, Jianghai Zhu, Forrest Hoyt, Randy R Miller, Julie Ehrhart, Christopher W Boyce, Katherine Young and 22 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Ribosome hibernation in zinc-starvedMicrobiology spectrum · 2026
    Article
  2. Review
  3. 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

32 authors.

Brendan M CrowleyDiscovery Chemistry, Merck & Co., West Point, PA, USA. brendan_crowley@merck.com.ORCID http://orcid.org/0009-0001-6140-6499
Helena I BoshoffTuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-4333-206X
Aidan BovingTuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-0114-1254
Vee Y TanTuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA.
Jianghai ZhuResearch Technologies Branch, Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA.
Forrest HoytResearch Technologies Branch, Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA.
Randy R MillerDepartment of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Rahway, NJ, USA.
Julie EhrhartDepartment of Nonclinical Drug Safety, Merck & Co., West Point, PA, USA.
Christopher W BoyceDiscovery Pharmaceutical Sciences, Merck & Co., West Point, PA, USA.ORCID http://orcid.org/0009-0001-3739-1119
Katherine YoungInfectious Disease and Vaccines, Merck & Co., Rahway, NJ, USA.
Philippe G NantermetDiscovery Chemistry, Merck & Co., West Point, PA, USA.
Jing SuDiscovery Chemistry, Merck & Co., West Point, PA, USA.
Lihu YangDiscovery Chemistry, Merck & Co., West Point, PA, USA.
Ronald E PainterQuantitative Biosciences, Merck & Co., West Point, PA, USA.
Emily B CorcoranDiscovery Process Chemistry, Merck & Co., Rahway, NJ, USA.
Jason L HoarDepartment of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Rahway, NJ, USA.
Sangmi OhTuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-0895-1110
David L HoltzmanGates Medical Research Institute, Cambridge, MA, USA.
Micha LeviGates Medical Research Institute, Cambridge, MA, USA.
Aparna AndersonGates Medical Research Institute, Cambridge, MA, USA.
Monicah A OtienoGates Medical Research Institute, Cambridge, MA, USA.
Matthew ZimmermanHackensack Meridian Health, Nutley, NJ, USA.
Firat KayaHackensack Meridian Health, Nutley, NJ, USA.ORCID http://orcid.org/0000-0001-8655-2065
Lisa M MassoudiMycobacteria Research Laboratories, Colorado State University, Fort Collins, CO, USA.
Michelle E RameyMycobacteria Research Laboratories, Colorado State University, Fort Collins, CO, USA.
Allison A BaumanMycobacteria Research Laboratories, Colorado State University, Fort Collins, CO, USA.
Anne J LenaertsMycobacteria Research Laboratories, Colorado State University, Fort Collins, CO, USA.
Gregory T RoberstonMycobacteria Research Laboratories, Colorado State University, Fort Collins, CO, USA.ORCID http://orcid.org/0000-0001-7157-4034
Véronique DartoisHackensack Meridian Health, Nutley, NJ, USA.ORCID http://orcid.org/0000-0001-9470-5009
Charles D WellsGates Medical Research Institute, Cambridge, MA, USA.
Clifton E BarryTuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA. cbarry@niaid.nih.gov.ORCID http://orcid.org/0000-0002-2927-270X
David B OlsenInfectious Disease and Vaccines, Merck & Co., Rahway, NJ, USA.ORCID http://orcid.org/0000-0001-5521-0206

Funding

Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID) AI000693Gates Foundation INV-001727
6 · The paper itself

Abstract

Linezolid, an oxazolidinone, is a cornerstone of treatment regimens for highly drug-resistant tuberculosis but cannot be used in drug-susceptible disease because of toxicity. This toxicity results from inhibition of mammalian mitochondrial protein synthesis. Here we show the development of a new oxazolidinone, MK-7762, with antitubercular activity that is better than linezolid and limited mitochondrial protein synthesis inhibition. The cryogenic electron microscopy structure of the stalled mycobacterial ribosome with MK-7762 revealed the basis for this selectivity. BALB/c mouse models of disease showed MK-7762 reduced lung bacterial burden by a 3-log-fold decrease in an acute model (N = 18) and a 2-log-fold decrease in chronically infected animals (N = 18). MK-7762 showed lesion penetration similar to linezolid in C3HeB/FeJ mice. MK-7762 had pharmacokinetic properties predicting low once-daily doses in humans and a favorable 14-day preclinical safety profile in Wistar Han rats (N = 30) and Beagle dogs (N = 6). Four-month safety studies in both rats (N = 20) and dogs (N = 24) showed no changes in hematology parameters at exposures well above the 100-mg predicted human dose. These data will enable MK-7762 to be explored as a component of new tuberculosis treatment combinations for all forms of the disease.

Indexed as

Antitubercular AgentsOxazolidinonesTuberculosisAcetamidesAnimalsDisease Models, AnimalDogsFemaleHumansLinezolidLungMiceMice, Inbred BALB CMice, Inbred C3HMycobacterium tuberculosisRatsAcetamidesAntitubercular AgentsLinezolidOxazolidinones

Identifiers

PMID41530381
PMCPMC12920096

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.