Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (740 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
Compounds which inhibit the synthesis of proteins. They are usually anti-bacterial agents or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Inhibitors, Protein Synthesis; Protein Synthesis Inhibitor; Inhibitor, Protein Synthesis; Synthesis Inhibitor, Protein; Protein Synthesis Antagonist; Antagonist, Protein Synthesis; Synthesis Antagonist, Protein; Protein Synthesis Antagonists.
Where it fits in the MeSH classification
- Broader topics
- Enzyme Inhibitors
Related concepts
- Anti-Bacterial Agents
Research landscape
PubMed indexes 9,790 records tagged with the MeSH heading “Protein Synthesis Inhibitors” (counts retrieved 2026-10-29). 248 of them (2.5%) were published from 2020 onward, and the busiest period so far is through 1999 with 4,473 records.
Reviews account for 296 records (3.0%) and meta-analyses for 4. Randomized controlled trials number 32 (0.3%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 4,473 |
| 2000-2009 | 3,764 |
| 2010-2019 | 1,305 |
| 2020 onward | 248 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 296 | 3.0% |
| Meta-analyses | 4 | 0.0% |
| Randomized controlled trials | 32 | 0.3% |
Method: PubMed query "Protein Synthesis Inhibitors"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in pharmacology
Drug evidence builds in layers: laboratory pharmacology describes how a compound acts, pharmacokinetic studies describe how the body handles it, and randomized trials test whether it helps and what harms it causes. Post-marketing surveillance and observational studies reveal rarer adverse effects but cannot prove causation. This page is educational and is not a recommendation to start, stop or change any medicine; decisions about treatment belong with a qualified clinician.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Linezolid Dose That Maximizes Sterilizing Effect While Minimizing Toxicity and Resistance Emergence for Tuberculosis | 2017 | Research article Design not recorded in structured metadata | 98 | cc by PMID 28584143 · DOI · PMC5527615 |
| Discovery of Novel Oral Protein Synthesis Inhibitors of Mycobacterium tuberculosis That Target Leucyl-tRNA Synthetase | 2016 | Research article Design not recorded in structured metadata | 94 | cc by PMID 27503647 · DOI · PMC5038265 |
| Puromycin reactivity does not accurately localize translation at the subcellular level | 2020 | Research article Design not recorded in structured metadata | 88 | cc by PMID 32844748 · DOI · PMC7490009 |
| Structural insights into context-dependent inhibitory mechanisms of chloramphenicol in cells | 2025 | Research article Design not recorded in structured metadata | 23 | cc by PMID 39668257 · DOI · PMC11832420 |
Linezolid Dose That Maximizes Sterilizing Effect While Minimizing Toxicity and Resistance Emergence for Tuberculosis [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Linezolid has an excellent sterilizing effect in tuberculosis patients but high adverse event rates.
- Closing excerpt
- The linezolid dose of 300 mg/day performed well and should be compared to 600 mg/day or 1,200 mg every other day in clinical trials.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (249 words)
Linezolid has an excellent sterilizing effect in tuberculosis patients but high adverse event rates. The dose that would maximize efficacy and minimize toxicity is unknown. We performed linezolid dose-effect and dose-scheduling studies in the hollow fiber system model of tuberculosis (HFS-TB) for sterilizing effect. HFS-TB units were treated with several doses to mimic human-like linezolid intrapulmonary pharmacokinetics and repetitively sampled for drug concentration, total bacterial burden, linezolid-resistant subpopulations, and RNA sequencing over 2 months. Linezolid-resistant isolates underwent whole-genome sequencing. The expression of genes encoding efflux pumps in the first 1 to 2 weeks revealed the same exposure-response patterns as the linezolid-resistant subpopulation. Linezolid-resistant isolates from the 2nd month of therapy revealed mutations in several efflux pump/transporter genes and a LuxR-family transcriptional regulator. Linezolid sterilizing effect was linked to the ratio of unbound 0- to 24-h area under the concentration-time curve (AUC0-24) to MIC. Optimal microbial kill was achieved at an AUC0-24/MIC ratio of 119. The optimal sterilizing effect dose for clinical use was identified using Monte Carlo simulations. Clinical doses of 300 and 600 mg/day (or double the dose every other day) achieved this target in 87% and >99% of 10,000 patients, respectively. The susceptibility breakpoint identified was 2 mg/liter. The simulations identified that a 300-mg/day dose did not achieve AUC0-24s associated with linezolid toxicity, while 600 mg/day achieved those AUC0-24s in <20% of subjects. The linezolid dose of 300 mg/day performed well and should be compared to 600 mg/day or 1,200 mg every other day in clinical trials.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 28584143 · DOI · PMC5527615
Discovery of Novel Oral Protein Synthesis Inhibitors of Mycobacterium tuberculosis That Target Leucyl-tRNA Synthetase [2]
Abstract reading summary — source excerpts
- Opening excerpt
- The recent development and spread of extensively drug-resistant and totally drug-resistant resistant (TDR) strains of Mycobacterium tuberculosis highlight the need for new antitubercular drugs.
- Closing excerpt
- tuberculosis Importantly, their good oral bioavailability translates into in vivo efficacy in both the acute and chronic mouse models of TB with potency comparable to that of the frontline drug isoniazid.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (185 words)
The recent development and spread of extensively drug-resistant and totally drug-resistant resistant (TDR) strains of Mycobacterium tuberculosis highlight the need for new antitubercular drugs. Protein synthesis inhibitors have played an important role in the treatment of tuberculosis (TB) starting with the inclusion of streptomycin in the first combination therapies. Although parenteral aminoglycosides are a key component of therapy for multidrug-resistant TB, the oxazolidinone linezolid is the only orally available protein synthesis inhibitor that is effective against TB. Here, we show that small-molecule inhibitors of aminoacyl-tRNA synthetases (AARSs), which are known to be excellent antibacterial protein synthesis targets, are orally bioavailable and effective against M. tuberculosis in TB mouse infection models. We applied the oxaborole tRNA-trapping (OBORT) mechanism, which was first developed to target fungal cytoplasmic leucyl-tRNA synthetase (LeuRS), to M. tuberculosis LeuRS. X-ray crystallography was used to guide the design of LeuRS inhibitors that have good biochemical potency and excellent whole-cell activity against M. tuberculosis Importantly, their good oral bioavailability translates into in vivo efficacy in both the acute and chronic mouse models of TB with potency comparable to that of the frontline drug isoniazid.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 27503647 · DOI · PMC5038265
Puromycin reactivity does not accurately localize translation at the subcellular level [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Puromycin is a tyrosyl-tRNA mimic that blocks translation by labeling and releasing elongating polypeptide chains from translating ribosomes.
- Closing excerpt
- Our findings urge caution when interpreting puromycylation assays in vivo.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (150 words)
Puromycin is a tyrosyl-tRNA mimic that blocks translation by labeling and releasing elongating polypeptide chains from translating ribosomes. Puromycin has been used in molecular biology research for decades as a translation inhibitor. The development of puromycin antibodies and derivatized puromycin analogs has enabled the quantification of active translation in bulk and single-cell assays. More recently, in vivo puromycylation assays have become popular tools for localizing translating ribosomes in cells. These assays often use elongation inhibitors to purportedly inhibit the release of puromycin-labeled nascent peptides from ribosomes. Using in vitro and in vivo experiments in various eukaryotic systems, we demonstrate that, even in the presence of elongation inhibitors, puromycylated peptides are released and diffuse away from ribosomes. Puromycylation assays reveal subcellular sites, such as nuclei, where puromycylated peptides accumulate post-release and which do not necessarily coincide with sites of active translation. Our findings urge caution when interpreting puromycylation assays in vivo.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 32844748 · DOI · PMC7490009
Structural insights into context-dependent inhibitory mechanisms of chloramphenicol in cells [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Ribosome-targeting antibiotics represent an important class of antimicrobial drugs.
- Closing excerpt
- This work exemplifies how in-cell structural biology can expand the understanding of mechanisms of action for extensively studied antibiotics.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (156 words)
Ribosome-targeting antibiotics represent an important class of antimicrobial drugs. Chloramphenicol (Cm) is a well-studied ribosomal peptidyl transferase center (PTC) binder and growing evidence suggests that its inhibitory action depends on the sequence of the nascent peptide. How such selective inhibition on the molecular scale manifests on the cellular level remains unclear. Here, we use cryo-electron tomography to analyze the impact of Cm inside the bacterium Mycoplasma pneumoniae. By resolving the Cm-bound ribosomes to 3.0 Å, we elucidate Cm's coordination with natural nascent peptides and transfer RNAs in the PTC. We find that Cm leads to the accumulation of a number of translation elongation states, indicating ongoing futile accommodation cycles, and to extensive ribosome collisions. We, thus, suggest that, beyond its direct inhibition of protein synthesis, the action of Cm may involve the activation of cellular stress responses. This work exemplifies how in-cell structural biology can expand the understanding of mechanisms of action for extensively studied antibiotics.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 39668257 · DOI · PMC11832420
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Linezolid: a review of its properties, function, and use in critical care [5]
- Research article Oxazolidinone antibiotics [6]
- Research article The A-Z of bacterial translation inhibitors [7]
- Research article Measuring protein synthesis with SUnSET: a valid alternative to traditional techniques? [8]
- Research article Ribosome-inactivating proteins [9]
- Research article The 2-5A system: modulation of viral and cellular processes through acceleration of RNA degradation [10]
References
- Srivastava S, Magombedze G, Koeuth T, Sherman C, Pasipanodya JG, Raj P, et al.. Linezolid Dose That Maximizes Sterilizing Effect While Minimizing Toxicity and Resistance Emergence for Tuberculosis. . 2017. PMID 28584143 · DOI · PMC5527615
- Palencia A, Li X, Bu W, Choi W, Ding CZ, Easom EE, et al.. Discovery of Novel Oral Protein Synthesis Inhibitors of Mycobacterium tuberculosis That Target Leucyl-tRNA Synthetase. . 2016. PMID 27503647 · DOI · PMC5038265
- Enam SU, Zinshteyn B, Goldman DH, Cassani M, Livingston NM, Seydoux G, et al.. Puromycin reactivity does not accurately localize translation at the subcellular level. . 2020. PMID 32844748 · DOI · PMC7490009
- Xue L, Spahn CMT, Schacherl M, Mahamid J. Structural insights into context-dependent inhibitory mechanisms of chloramphenicol in cells. . 2025. PMID 39668257 · DOI · PMC11832420
- Hashemian SMR, Farhadi T, Ganjparvar M. Linezolid: a review of its properties, function, and use in critical care. Drug Des Devel Ther. 2018. PMID 29950810 · DOI · PMC6014438
- Diekema DJ, Jones RN. Oxazolidinone antibiotics. Lancet. 2001. PMID 11747939 · DOI
- Wilson DN. The A-Z of bacterial translation inhibitors. Crit Rev Biochem Mol Biol. 2009. PMID 19929179 · DOI
- Goodman CA, Hornberger TA. Measuring protein synthesis with SUnSET: a valid alternative to traditional techniques?. Exerc Sport Sci Rev. 2013. PMID 23089927 · DOI · PMC3951011
- Stirpe F. Ribosome-inactivating proteins. Toxicon. 2004. PMID 15302521 · DOI
- Player MR, Torrence PF. The 2-5A system: modulation of viral and cellular processes through acceleration of RNA degradation. Pharmacol Ther. 1998. PMID 9623881 · DOI · PMC7157933
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.