Evidence map›Paper›PMID 41435821›Full record

ArticleCell2026

Mapping cellular targets of covalent cancer drugs in the entire mammalian body.

Zhengyuan Pang, Verina H Leung, Cailynn C Wang, Ahmadreza Attarpour, Anthony Rinaldi, Hanbing Shen, Maria Dolores Moya-Garzon, Logan H Sigua, Claire Rammel, Alexandra Selke and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Chemical Biology 2025: Highlights From the Ch/Bi145 Course at Caltech.Chembiochem : a European journal of chemical biology · 2026
    Review
  3. 2-Alkyl Furans Undergo Radiolytic Oxidative Protein Cross-Linking.Journal of the American Chemical Society · 2026
    Article
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Zhengyuan PangDepartment of Neuroscience, Dorris Neuroscience Center, Scripps Research, San Diego, CA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA; Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.
Verina H LeungDepartment of Neuroscience, Dorris Neuroscience Center, Scripps Research, San Diego, CA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
Cailynn C WangDepartment of Neuroscience, Dorris Neuroscience Center, Scripps Research, San Diego, CA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
Ahmadreza AttarpourPhysical Sciences Platform, Sunnybrook Research Institute, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
Anthony RinaldiPhysical Sciences Platform, Sunnybrook Research Institute, Toronto, ON, Canada.
Hanbing ShenDepartment of Neuroscience, Dorris Neuroscience Center, Scripps Research, San Diego, CA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
Maria Dolores Moya-GarzonDepartment of Pathology, Stanford School of Medicine, Stanford, CA, USA; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
Logan H SiguaDepartment of Neuroscience, Dorris Neuroscience Center, Scripps Research, San Diego, CA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
Claire RammelSection of Cardio-Oncology & Immunology, Cardiovascular Research Institute (CVRI), University of California, San Francisco, School of Medicine, San Francisco, CA 94158, USA.
Alexandra SelkeDepartment of Neuroscience, Dorris Neuroscience Center, Scripps Research, San Diego, CA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
Christopher GlynnDepartment of Neuroscience, Dorris Neuroscience Center, Scripps Research, San Diego, CA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
Melaina YenderDepartment of Neuroscience, Dorris Neuroscience Center, Scripps Research, San Diego, CA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
Senhan XuDepartment of Neuroscience, Dorris Neuroscience Center, Scripps Research, San Diego, CA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
Javid J MoslehiSection of Cardio-Oncology & Immunology, Cardiovascular Research Institute (CVRI), University of California, San Francisco, School of Medicine, San Francisco, CA 94158, USA.
Peng WuDepartment of Molecular and Cellular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Jonathan Z LongDepartment of Pathology, Stanford School of Medicine, Stanford, CA, USA; Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
Maged GoubranPhysical Sciences Platform, Sunnybrook Research Institute, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada; Hurvitz Brain Sciences, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Benjamin F CravattDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.
Li YeDepartment of Neuroscience, Dorris Neuroscience Center, Scripps Research, San Diego, CA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA. Electronic address: liye@scripps.edu.

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007198 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHI, NEIL C, INSEL, PAUL A · 1985 to 2024
$29.3M
Project 3 (Mercola)P01HL141084 · NHLBI · STANFORD UNIVERSITY · PI Joseph C. Wu · 2019 to 2026
$21.1M
MULTIDISCIPLINARY BASIC RESEARCH TRAINING IN CANCERT32CA009592 · NCI · VANDERBILT UNIVERSITY · PI Justin M Balko, Julie A Rhoades (Sterling) · 1987 to 2026
$10.4M
Immunologic and Antigenic Drivers of Immune Checkpoint Inhibitor-Associated MyocarditisR01HL156021 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Justin M Balko, Javid J Moslehi · 2021 to 2026
$4.9M
Chemoenzymatic glycan editing for deciphering biological functions of glycansR35GM139643 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI Peng Wu · 2021 to 2026
$4.7M
Novel mechanisms and predictors of VEGF receptor inhibitor-associated hypertensionR01HL141466 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MOSLEHI, JAVID J · 2019 to 2023
$3.3M
Mapping brain-wide opioid actions by profiling neuronal activities and in vivo cellular target engagementR01DA059393 · NIDA · SCRIPPS RESEARCH INSTITUTE, THE · PI Laura M. Bohn, Ryan Ashok Shenvi · 2023 to 2026
$3.3M
Long-Term Cardiovascular Sequelae of Cancer ImmunotherapiesR01HL155990 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI JOHNSON, DOUGLAS B, MOSLEHI, JAVID J · 2021 to 2025
$3.3M
Modulating somatosensory network to target metabolic diseasesDP2DK128800 · NIDDK · SCRIPPS RESEARCH INSTITUTE, THE · PI YE, LI · 2020 to 2020
$2.7M
A platform to identify in vivo targets of covalent cancer drugs in 3D tissuesR33CA281918 · NCI · SCRIPPS RESEARCH INSTITUTE, THE · PI CRAVATT, BENJAMIN F, YE, LI · 2023 to 2025
$1.3M
NCI NIH HHS R33 CA281918NCI NIH HHS T32 CA009592NHLBI NIH HHS P01 HL141084NHLBI NIH HHS R01 HL141466NHLBI NIH HHS R01 HL155990NHLBI NIH HHS R01 HL156021NIDA NIH HHS R01 DA059393NIDDK NIH HHS DP2 DK128800NIGMS NIH HHS R35 GM139643NIGMS NIH HHS T32 GM007198
6 · The paper itself

Abstract

As our understanding of biological systems reaches single-cell and high spatial resolutions, it becomes imperative that pharmacological approaches match this precision to understand drug actions. This need is particularly urgent for the targeted covalent inhibitors that are currently re-entering the stage for cancer treatments. By leveraging the unique kinetics of click reactions, we developed volumetric clearing-assisted tissue click chemistry (vCATCH) to enable deep and homogeneous click labeling across the three-dimensional (3D) mammalian body. With simple and passive incubation steps, vCATCH offers cellular-resolution drug imaging in the entire adult mouse. We combined vCATCH with hydrogel-based reinforcement of three-dimensional imaging solvent-cleared organs (HYBRiD) imaging and virtual reality to visualize and quantify in vivo targets of two clinical cancer drugs, afatinib and ibrutinib, which recapitulated their known pharmacological distribution and revealed previously unreported tissue and cell-type engagement potentially linked to off-target effects. vCATCH provides a body-wide, unbiased platform to map covalent drug engagements at unprecedented scale and precision.

Indexed as

Antineoplastic AgentsNeoplasmsAdenineAfatinibAnimalsCell Line, TumorClick ChemistryFemaleHumansImaging, Three-DimensionalMicePiperidinesPyrazolesPyrimidinesAdenineAfatinibAntineoplastic AgentsibrutinibPiperidinesPyrazolesPyrimidinesdrug targetstargeted covalent inhibitorstissue clearingwhole-body imaging

Identifiers

PMID41435821
PMCPMC12875305

What OpenQuestion 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 OpenQuestion graph.