Evidence map›Paper›PMID 24950332›Full record

ArticleNature chemistry2014

Imaging the intracellular distribution of tyrosine kinase inhibitors in living cells with quantitative hyperspectral stimulated Raman scattering.

Dan Fu, Jing Zhou, Wenjing Suzanne Zhu, Paul W Manley, Y Karen Wang, Tami Hood, Andrew Wylie, X Sunney Xie

Registry-linked trialAbstract read
In one paragraph

Article in Nature chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04394416 (Randomized Double-Blind Placebo-Controlled Trial on the Safety and Efficacy of Imatinib for Hospitalized Adults With COVID-19), which is not on this map. Cited by 126 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
126citing papers in PubMed, 1 pooled it
–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.

NCT04394416 phase3terminatednot on this mapstarted 2020, after this paper: background citation

Randomized Double-Blind Placebo-Controlled Trial on the Safety and Efficacy of Imatinib for Hospitalized Adults With COVID-19

TypeinterventionalSponsorUniversity of Maryland, BaltimoreRan2020 to 2025Enrolled21ConditionsCOVID-19ArmsImatinib, Placebo oral tablet
3 · Its place in the literature

Who cites it

126 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Targeting Lysosomes for Enhanced Anti-Cancer Therapeutics and Immune Response.International journal of biological sciences · 2026
    Review
  9. Bond-Selective Imaging at the Frontier of Biomedicine.Chemical & biomedical imaging · 2025
    Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
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  20. Review

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

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

8 authors.

Dan Fu1] Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA [2].
Jing Zhou1] Novartis Institute for Biomedical Research, Cambridge, Massachusetts 02139, USA [2].
Wenjing Suzanne ZhuNovartis Institute for Biomedical Research, Cambridge, Massachusetts 02139, USA.
Paul W ManleyNovartis Institute for Biomedical Research, Basel CH-4002, Switzerland.
Y Karen WangNovartis Institute for Biomedical Research, Cambridge, Massachusetts 02139, USA.
Tami HoodNovartis Institute for Biomedical Research, Cambridge, Massachusetts 02139, USA.
Andrew WylieNovartis Institute for Biomedical Research, Cambridge, Massachusetts 02139, USA.
X Sunney XieDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.

Funding

Imaging the Invisible with No Labels: A Major Opportunity in Biology and MedicineR01EB010244 · NIBIB · HARVARD UNIVERSITY · PI XIE, XIAOLIANG SUNNEY · 2009 to 2013
$3.9M
NIBIB NIH HHS 1R01EB010244-01NIBIB NIH HHS R01 EB010244
6 · The paper itself

Abstract

ABL1 tyrosine-kinase inhibitors (TKI) are front-line therapy for chronic myelogenous leukaemia and are among the best-known examples of targeted cancer therapeutics. However, the dynamic uptake into cells of TKIs of low molecular weight and their intracellular behaviour is unknown because of the difficulty of observing non-fluorescent small molecules at subcellular resolution. Here we report the direct label-free visualization and quantification of two TKI drugs (imatinib and nilotinib) inside living cells using hyperspectral stimulated Raman scattering imaging. Concentrations of both drugs were enriched over 1,000-fold in lysosomes as a result of their lysosomotropic properties. In addition, low solubility appeared to contribute significantly to the surprisingly large accumulation of nilotinib. We further show that the lysosomal trapping of imatinib was reduced more than tenfold when chloroquine is used simultaneously, which suggests that chloroquine may increase the efficacy of TKIs through lysosome-mediated drug-drug interaction in addition to the commonly proposed autophagy-inhibition mechanism.

Indexed as

Cell TrackingEukaryotic CellsHumansMicroscopy, ConfocalProtein Kinase InhibitorsSpectrum Analysis, RamanProtein Kinase Inhibitors

Identifiers

PMID24950332
PMCPMC4205760

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Registered trials

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.