Evidence map›Paper›PMID 39138346›Full record

ArticleNature chemistry2024

Multi-tiered chemical proteomic maps of tryptoline acrylamide-protein interactions in cancer cells.

Evert Njomen, Rachel E Hayward, Kristen E DeMeester, Daisuke Ogasawara, Melissa M Dix, Tracey Nguyen, Paige Ashby, Gabriel M Simon, Stuart L Schreiber, Bruno Melillo and 1 more

Abstract read
In one paragraph

Article in Nature chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing 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

41 citing papers in PubMed.

  1. Review
  2. A safety pin against BAX.Nature chemical biology · 2026
    Article
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  13. Targeting extrachromosomal DNA in human cancers.Nature reviews. Drug discovery · 2026
    Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Integrated phenotypic screening and chemical proteomics identifies ETF1 ligands that modulate viral translation and replication.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  20. 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

11 authors.

Evert NjomenDepartment of Chemistry, Scripps Research, La Jolla, CA, USA. enjomen@scripps.edu.ORCID 0000-0002-3508-2638
Rachel E HaywardDepartment of Chemistry, Scripps Research, La Jolla, CA, USA.ORCID 0000-0002-1080-8244
Kristen E DeMeesterDepartment of Chemistry, Scripps Research, La Jolla, CA, USA.
Daisuke OgasawaraDepartment of Chemistry, Scripps Research, La Jolla, CA, USA.ORCID 0000-0002-2178-4698
Melissa M DixDepartment of Chemistry, Scripps Research, La Jolla, CA, USA.
Tracey NguyenVividion Therapeutics, San Diego, CA, USA.
Paige AshbyVividion Therapeutics, San Diego, CA, USA.
Gabriel M SimonVividion Therapeutics, San Diego, CA, USA.
Stuart L SchreiberChemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, MA, USA.
Bruno MelilloDepartment of Chemistry, Scripps Research, La Jolla, CA, USA. bmelillo@scripps.edu.ORCID 0000-0002-9708-5287
Benjamin F CravattDepartment of Chemistry, Scripps Research, La Jolla, CA, USA. cravatt@scripps.edu.ORCID 0000-0001-5330-3492

Funding

RP5: Chemical proteomic discovery of small-molecule probes for autophagy proteinsU19AI142784 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI CRAVATT, BENJAMIN F · 2019 to 2023
$36.9M
Chemical Proteomic Platforms for Radically Expanding Cancer DruggabilityR35CA231991 · NCI · SCRIPPS RESEARCH INSTITUTE, THE · PI BENJAMIN F CRAVATT · 2018 to 2026
$9.5M
eDyNAmiC - STANFORDOT2CA278688 · NCI · STANFORD UNIVERSITY · PI PAUL S MISCHEL · 2022 to 2026
$7.7M
eDyNAmiC - SCRIPPSOT2CA278692 · NCI · SCRIPPS RESEARCH INSTITUTE, THE · PI BENJAMIN F CRAVATT · 2022 to 2026
$2.1M
Cancer Research UK CGCATF-2021/100012Cancer Research UK (CRUK) CGCATF-2021/100021Howard Hughes Medical Institute (HHMI) GT15176NCI NIH HHS OT2 CA278688NCI NIH HHS OT2 CA278692NCI NIH HHS R35 CA231991NIAID NIH HHS U19 AI142784
6 · The paper itself

Abstract

Covalent chemistry is a versatile approach for expanding the ligandability of the human proteome. Activity-based protein profiling (ABPP) can infer the specific residues modified by electrophilic compounds through competition with broadly reactive probes. However, the extent to which such residue-directed platforms fully assess the protein targets of electrophilic compounds in cells remains unclear. Here we evaluate a complementary protein-directed ABPP method that identifies proteins showing stereoselective reactivity with alkynylated, chiral electrophilic compounds-termed stereoprobes. Integration of protein- and cysteine-directed data from cancer cells treated with tryptoline acrylamide stereoprobes revealed generally well-correlated ligandability maps and highlighted features, such as protein size and the proteotypicity of cysteine-containing peptides, that explain gaps in each ABPP platform. In total, we identified stereoprobe binding events for >300 structurally and functionally diverse proteins, including compounds that stereoselectively and site-specifically disrupt MAD2L1BP interactions with the spindle assembly checkpoint complex leading to delayed mitotic exit in cancer cells.

Indexed as

AcrylamideProteomicsCarbolinesCell Line, TumorHumansProtein BindingProteomeStereoisomerismTryptaminesAcrylamideCarbolinesProteomeTryptaminestryptoline

Identifiers

PMID39138346
PMCPMC11684312

What OpenQuestion holds

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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 OpenQuestion graph.