Evidence map›Paper›PMID 41735331›Full record

ArticleNature communications2026

Context-dependent translation inhibition as a cancer therapeutic modality.

Paige D Diamond, Paul V Sauer, Mikael Holm, Canessa J Swanson-Swett, Lucas Ferguson, Natalie M Bratset, Grant W Wienker, Justin Seiwert Sim, Hailey K Adams, Lillian Kenner and 6 more

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Review
  2. Quantitative profiling of basal and stress-induced ribosome collisions.bioRxiv : the preprint server for biology · 2026
    Article
  3. Approaches for Studying Context Specificity of Translation Inhibitor Action.International journal of molecular sciences · 2026
    Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. 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

16 authors.

Paige D Diamond *Interdict Bio Inc., South San Francisco, CA, USA.
Paul V Sauer *Interdict Bio Inc., South San Francisco, CA, USA.ORCID 0000-0001-7204-5863
Mikael Holm *Interdict Bio Inc., South San Francisco, CA, USA.
Canessa J Swanson-SwettInterdict Bio Inc., South San Francisco, CA, USA.
Lucas FergusonInterdict Bio Inc., South San Francisco, CA, USA.
Natalie M BratsetInterdict Bio Inc., South San Francisco, CA, USA.ORCID 0009-0003-3858-3432
Grant W WienkerInterdict Bio Inc., South San Francisco, CA, USA.
Justin Seiwert SimInterdict Bio Inc., South San Francisco, CA, USA.
Hailey K AdamsInterdict Bio Inc., South San Francisco, CA, USA.
Lillian KennerInterdict Bio Inc., South San Francisco, CA, USA.
Margot MeyersInterdict Bio Inc., South San Francisco, CA, USA.
David GygiInterdict Bio Inc., South San Francisco, CA, USA.
Zef A KönstInterdict Bio Inc., South San Francisco, CA, USA.
Sogole Sami BahmanyarInterdict Bio Inc., South San Francisco, CA, USA.
Lawrence G HamannInterdict Bio Inc., South San Francisco, CA, USA.
Anthony P SchullerInterdict Bio Inc., South San Francisco, CA, USA. aschuller@interdictbio.com.ORCID 0000-0003-3098-3055

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Recent work has demonstrated that some bacterial antibiotics that inhibit protein synthesis by binding the peptidyl transferase center (PTC) of the ribosome act in a context-dependent manner, inhibiting translation elongation only at specific amino acids. However, this phenomenon has yet to be documented for compounds that inhibit the PTC of the human ribosome. Here, we use structure-based design to guide the synthesis of such PTC-binding, context-dependent inhibitors of the human ribosome, termed interdictors. In the PTC, these compounds preferentially interact with nascent protein residues that exhibit complementary physiochemical properties to the moieties of the small molecule, causing structural rearrangements in both the nascent polypeptide chain and ribosomal RNA. Further, the compounds differentially impact ribosome surveillance pathways, including the ribotoxic stress response. Finally, we confirm their anti-tumor activity after oral dosing in a mouse xenograft model of triple-negative breast cancer. Together, our data establish targeting oncogenic dependency factors through context-dependent inhibition of translation as a potential small molecule therapeutic modality for historically difficult to address cancers.

Indexed as

Antineoplastic AgentsProtein BiosynthesisProtein Synthesis InhibitorsRibosomesTriple Negative Breast NeoplasmsAnimalsCell Line, TumorFemaleHumansMicePeptidyl TransferasesRNA, RibosomalXenograft Model Antitumor AssaysAntineoplastic AgentsPeptidyl TransferasesProtein Synthesis InhibitorsRNA, Ribosomal

Identifiers

PMID41735331
PMCPMC12932737

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.