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Related Experiment Video

Updated: May 25, 2025

Visualization of Metabolites Identified in the Spatial Metabolome of Traditional Chinese Medicine Using DESI-MSI
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Mitigating Nephrotoxicity Risks and Ranking Drug Candidates Using MALDI Mass Spectrometry Imaging: A Case Study.

Bingming Chen1, Lisa LaFranco-Scheuch1, Shuzhi Dong1

  • 1Merck & Co., Inc., Rahway, New Jersey, USA.

Toxicologic Pathology
|February 27, 2025
PubMed
Summary
This summary is machine-generated.

Drug-induced kidney damage is a significant hurdle in drug development. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) helps predict and prevent this by mapping drug distribution in kidneys.

Keywords:
MALDIdrug discoverylead optimizationmass spectrometry imagingnephrotoxicity

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Area of Science:

  • Pharmacology
  • Toxicology
  • Analytical Chemistry

Background:

  • Drug-induced nephrotoxicity is a major challenge, causing nearly 25% of severe adverse effects.
  • Antimicrobial drugs are implicated in one-third of nephrotoxicity cases.
  • Observed nephrotoxicity (renal tubule degeneration, tubular casts) during antibacterial lead optimization.

Purpose of the Study:

  • To investigate nephrotoxicity mechanisms and triage drug candidates.
  • To utilize matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) for spatial localization of compounds in kidney tissues.
  • To establish a correlation between drug distribution and observed nephrotoxicity.

Main Methods:

  • Employed MALDI-MSI to analyze compound distribution in rat kidney sections.
  • Compared renal distribution patterns of toxic versus non-toxic drug candidates.
  • Correlated compound localization with in vivo nephrotoxicity data.

Main Results:

  • MALDI-MSI enabled label-free spatial localization of drugs and metabolites in kidney tissues.
  • A correlation was found between preferential distribution in the renal cortex/outer medulla and positive in vivo nephrotoxicity for most candidates.
  • This correlation aided in ranking compounds for antimicrobial drug discovery.

Conclusions:

  • MALDI-MSI is a powerful tool for investigating drug distribution and nephrotoxicity mechanisms.
  • The established correlation can facilitate compound triage and derisking during drug discovery and development.
  • MALDI-MSI offers a pathway to mitigate drug-induced nephrotoxicity risks.