Evidence map›Paper›PMID 38724853›Full record

ArticleMolecular systems biology2024

An integrative epigenome-based strategy for unbiased functional profiling of clinical kinase inhibitors.

Francesco Gualdrini, Stefano Rizzieri, Sara Polletti, Francesco Pileri, Yinxiu Zhan, Alessandro Cuomo, Gioacchino Natoli

Abstract read
In one paragraph

Article in Molecular systems biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Review
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

7 authors.

Francesco GualdriniDepartment of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milano, 20139, Italy. francesco.gualdrini@ieo.it.ORCID http://orcid.org/0000-0002-6180-7292
Stefano Rizzieri *Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milano, 20139, Italy.
Sara Polletti *Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milano, 20139, Italy.ORCID http://orcid.org/0000-0002-5433-0502
Francesco Pileri *Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milano, 20139, Italy.
Yinxiu ZhanDepartment of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milano, 20139, Italy.ORCID http://orcid.org/0000-0001-7702-6207
Alessandro CuomoDepartment of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milano, 20139, Italy.ORCID http://orcid.org/0000-0002-9778-7190
Gioacchino NatoliDepartment of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milano, 20139, Italy. gioacchino.natoli@ieo.it.ORCID http://orcid.org/0000-0003-0711-2411

Funding

EC | European Research Council (ERC) 692789EC | Horizon Europe | Excellent Science | HORIZON EUROPE Marie Sklodowska-Curie Actions (MSCA) 789792
6 · The paper itself

Abstract

More than 500 kinases are implicated in the control of most cellular process in mammals, and deregulation of their activity is linked to cancer and inflammatory disorders. 80 clinical kinase inhibitors (CKIs) have been approved for clinical use and hundreds are in various stages of development. However, CKIs inhibit other kinases in addition to the intended target(s), causing both enhanced clinical effects and undesired side effects that are only partially predictable based on in vitro selectivity profiling. Here, we report an integrative approach grounded on the use of chromatin modifications as unbiased, information-rich readouts of the functional effects of CKIs on macrophage activation. This approach exceeded the performance of transcriptome-based approaches and allowed us to identify similarities and differences among CKIs with identical intended targets, to recognize novel CKI specificities and to pinpoint CKIs that may be repurposed to control inflammation, thus supporting the utility of this strategy to improve selection and use of CKIs in clinical settings.

Indexed as

EpigenomeProtein Kinase InhibitorsAnimalsHumansMacrophage ActivationMacrophagesMiceProtein Kinase InhibitorsClinical Kinase InhibitorsDrug RepurposingEpigenomeInflammationMachine Learning

Identifiers

PMID38724853
PMCPMC11148061

What Socratic holds

Textmetadata
LicenceCC BY
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.