ArticlePLoS biology2017
Selective stalling of human translation through small-molecule engagement of the ribosome nascent chain.
Article in PLoS biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 61 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 125 citations in OpenAlex.
- Pooled it
- Halting translation by the letter with sequence-selective small molecules.Nature chemical biology · 2026Review
- Quantitative profiling of basal and stress-induced ribosome collisions.bioRxiv : the preprint server for biology · 2026Article
- Approaches for Studying Context Specificity of Translation Inhibitor Action.International journal of molecular sciences · 2026Review
- Translational resistance to amino acid starvation in breast cancer cells revealed by ribosome profiling.iScience · 2026Article
- Triterpenoids and Lignans From Schisandra henryi subsp. yunnanensis A. C. Smith.Chemistry & biodiversity · 2026Article
- RiboScreenBiomedicines · 2026Review
- Context-dependent translation inhibition as a cancer therapeutic modality.Nature communications · 2026Article
- Sensitivity to an inhibitor of translation elongation in solid and hematologic cancers.Scientific reports · 2025Article
- PCSK9 promotes progression of anaplastic thyroid cancer through E-cadherin endocytosis.Cell death & disease · 2025Article
- Dysregulated ribosome quality control in human diseases.The FEBS journal · 2025Review
- SVC112: From Hummingbirds to Head and Neck Cancer.Advances in experimental medicine and biology · 2025Article
- Activity-Based DNA-Encoded Library Screening for Selective Inhibitors of Eukaryotic Translation.ACS central science · 2024Article
- Ribosome decision graphs for the representation of eukaryotic RNA translation complexity.Genome research · 2024Article
- Enhancing the Small-Scale Screenable Biological Space beyond Known Chemogenomics Libraries with Gray Chemical Matter─Compounds with Novel Mechanisms from High-Throughput Screening Profiles.ACS chemical biology · 2024Article
- Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): from bench to bedside.Signal transduction and targeted therapy · 2024Review
- Gut ribotoxic stress responses facilitate dyslipidemia via metabolic reprogramming: an environmental health prediction.Theranostics · 2024Article
- Ribosome Decision Graphs for the Representation of Eukaryotic RNA Translation Complexity.bioRxiv : the preprint server for biology · 2023Article
- Motif-ation matters.Nature chemical biology · 2023Article
- Control of mRNA fate by its encoded nascent polypeptide.Molecular cell · 2023Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in regulating the levels of plasma low-density lipoprotein cholesterol (LDL-C). Here, we demonstrate that the compound PF-06446846 inhibits translation of PCSK9 by inducing the ribosome to stall around codon 34, mediated by the sequence of the nascent chain within the exit tunnel. We further show that PF-06446846 reduces plasma PCSK9 and total cholesterol levels in rats following oral dosing. Using ribosome profiling, we demonstrate that PF-06446846 is highly selective for the inhibition of PCSK9 translation. The mechanism of action employed by PF-06446846 reveals a previously unexpected tunability of the human ribosome that allows small molecules to specifically block translation of individual transcripts.
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What OpenQuestion holds
Registered trials
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.