4.7 Article

Utilizing Stimulated Raman Scattering Microscopy To Study Intracellular Distribution of Label-Free Ponatinib in Live Cells

Journal

JOURNAL OF MEDICINAL CHEMISTRY
Volume 63, Issue 5, Pages 2028-2034

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.9b01546

Keywords

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Funding

  1. EPSRC [EP/L016559/1]
  2. MRC (OPTIMA CDT Studentship) [EP/L016559/1]
  3. Cancer Research UK [C157/A25140, C157/A15703]
  4. UK Regenerative Medicine Platform Niche Hub, MRC grant [MR/K026666/1]
  5. MRC [MR/K026666/1] Funding Source: UKRI

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Stimulated Raman scattering (SRS) microscopy represents a powerful method for imaging label-free drug distribution with high resolution. SRS was applied to image label-free ponatinib with high sensitivity and specificity in live human chronic myeloid leukemia (CML) cell lines. This was achieved at biologically relevant, nanomolar concentrations, allowing determination of ponatinib uptake and sequestration into lysosomes during the development of acquired drug resistance and an improved understanding of target engagement.

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