Evidence map›Paper›PMID 36593396›Full record

ArticleNature biotechnology2023

A proteome-wide atlas of drug mechanism of action.

Dylan C Mitchell, Miljan Kuljanin, Jiaming Li, Jonathan G Van Vranken, Nathan Bulloch, Devin K Schweppe, Edward L Huttlin, Steven P Gygi

Open access · greenAbstract read
In one paragraph

Article in Nature biotechnology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed, 1 pooled it
21.2field-weighted citation impact, top 1% of its field
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

86 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.

  1. Pooled it
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  13. Single-Injection Multi-Omics Analysis by Direct Infusion Mass Spectrometry.Angewandte Chemie (International ed. in English) · 2026
    Article
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  19. A Framework for Autonomous AI-Driven Drug Discovery.bioRxiv : the preprint server for biology · 2026
    Article
  20. Article

26 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Dylan C MitchellDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.
Miljan KuljaninDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.
Jiaming LiDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9065-6913
Jonathan G Van VrankenDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.
Nathan BullochDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.
Devin K SchweppeDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-3241-6276
Edward L HuttlinDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1822-1173
Steven P GygiDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA. steven_gygi@hms.harvard.edu.ORCID http://orcid.org/0000-0001-7626-0034
Harvard University · USUniversity of Washington · US

Funding

New Sample Multiplexing Technologies to Identify Chemical Probes and Illuminate Ubiquitin BiologyR01GM067945 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI GYGI, STEVEN P · 2003 to 2024
$10.5M
NIGMS NIH HHS R01 GM067945
6 · The paper itself

Abstract

Defining the cellular response to pharmacological agents is critical for understanding the mechanism of action of small molecule perturbagens. Here, we developed a 96-well-plate-based high-throughput screening infrastructure for quantitative proteomics and profiled 875 compounds in a human cancer cell line with near-comprehensive proteome coverage. Examining the 24-h proteome changes revealed ligand-induced changes in protein expression and uncovered rules by which compounds regulate their protein targets while identifying putative dihydrofolate reductase and tankyrase inhibitors. We used protein-protein and compound-compound correlation networks to uncover mechanisms of action for several compounds, including the adrenergic receptor antagonist JP1302, which we show disrupts the FACT complex and degrades histone H1. By profiling many compounds with overlapping targets covering a broad chemical space, we linked compound structure to mechanisms of action and highlighted off-target polypharmacology for molecules within the library.

Indexed as

NeoplasmsProteomeCell LineHigh-Throughput Screening AssaysHumansProteomicsProteome

Identifiers

PMID36593396
PMCPMC11069389
OpenAlexW4313453500

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.