Evidence map›Paper›PMID 41279551›Full record

ArticlebioRxiv : the preprint server for biology2025

Molecular Dynamics-Guided Design and Chemoproteomic Profiling of Covalent Kinase Activity Probes.

Pratyasha Chakraborty, Anthony Carlos, Trayder Thomas, Kyle Ghaby, Shaghayegh Fathi, Mukta Sharma, Ngoc Kim Nguyen, Mason Farmwald, Lydia Blachowicz, Shaopeng Yu and 3 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Pratyasha ChakrabortyDepartment of Chemistry, The University of Chicago, Chicago, IL, 60637, USA.
Anthony CarlosDepartment of Chemistry, The University of Chicago, Chicago, IL, 60637, USA.
Trayder ThomasDepartment of Biochemistry and Molecular Biophysics, The University of Chicago, Chicago, IL, 60637, USA.
Kyle GhabyDepartment of Biochemistry and Molecular Biophysics, The University of Chicago, Chicago, IL, 60637, USA.
Shaghayegh FathiDepartment of Chemistry, The University of Chicago, Chicago, IL, 60637, USA.
Mukta SharmaDepartment of Biochemistry and Molecular Biophysics, The University of Chicago, Chicago, IL, 60637, USA.
Ngoc Kim NguyenDepartment of Chemistry, The University of Chicago, Chicago, IL, 60637, USA.
Mason FarmwaldDepartment of Chemistry, The University of Chicago, Chicago, IL, 60637, USA.
Lydia BlachowiczDepartment of Biochemistry and Molecular Biophysics, The University of Chicago, Chicago, IL, 60637, USA.
Shaopeng YuDepartment of Chemistry, The University of Chicago, Chicago, IL, 60637, USA.
Kavya Smitha PillaiDepartment of Chemistry, The University of Chicago, Chicago, IL, 60637, USA.
Benoît RouxDepartment of Chemistry, The University of Chicago, Chicago, IL, 60637, USA.
Raymond MoelleringDepartment of Chemistry, The University of Chicago, Chicago, IL, 60637, USA.

Funding

Multi-Disciplinary Training Grant in Cancer ResearchT32CA009594 · NCI · UNIVERSITY OF CHICAGO · PI KAY F MACLEOD, Scott A. Oakes · 1989 to 2026
$11.5M
Conformational Flexibility in Activation of Src-KinaseR01CA093577 · NCI · WEILL MEDICAL COLLEGE OF CORNELL UNIV · PI BENOIT ROUX · 2002 to 2026
$5.6M
Beagle-3: A Shared GPU Cluster for Biomolecular SciencesS10OD028655 · OD · UNIVERSITY OF CHICAGO · PI ROUX, BENOIT · 2020 to 2020
$2.0M
Mapping Protein Social Network Dynamics with Photoproximity Profiling PlatformsR01GM145852 · NIGMS · UNIVERSITY OF CHICAGO · PI MOELLERING, RAYMOND E · 2022 to 2025
$1.5M
Single-Cell Protein Activity Profiling in Breast Cancer Cells and TissuesR33CA269094 · NCI · UNIVERSITY OF CHICAGO · PI MOELLERING, RAYMOND E · 2022 to 2024
$1.1M
NCI NIH HHS R01 CA093577NCI NIH HHS R33 CA269094NCI NIH HHS T32 CA009594NIGMS NIH HHS R01 GM145852NIH HHS S10 OD028655
6 · The paper itself

Abstract

Covalent small molecule activity probes can be powerful tools to interrogate protein function in native cellular environments. The design of family-wide activity probes requires an understanding of the molecular sources of general targeting potential and specificity to enable broad targeting of protein family members. Here, we developed and applied a multifaceted docking and molecular dynamics (MD) simulation pipeline to design and test cell-permeable covalent kinase activity probes from a set of hinge-binding pharmacophores. This computationally-guided approach yielded a new cell-active probe, K60P, which targets around 114 kinases across distinct kinase classes in live cells. Chemoproteomic profiling of this probe and a clinical candidate sharing the same indazole core, KW-2449, identified kinase and non-kinase target profiles that differ from recombinant protein assay profiles, underscoring the utility of native kinase profiling

Identifiers

PMID41279551
PMCPMC12633015

What OpenQuestion holds

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Registered trials

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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.