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March 25, 2026PharmaceuticalsOpen Access

Efficacious Anti-Cancer Drugs Targeting Nicotinamide N-Methyltransferase (NNMT) in Cultured Human Oral Squamous Cell Carcinoma (OSCC)

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Authors

BMBrian P. MaloneyMKMartyna KubisztalZGZiqian Ge

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Overview

Investigative study shows that targeting NNMT may improve anti-cancer strategies in oral squamous cell carcinoma, indicating its role in treatment.

Key Points

  • The aim is to evaluate novel inhibitors of NNMT for their effectiveness against OSCC and to explore their mechanisms of action.
  • Identified two NNMT inhibitors (AG-670 and AO-022) using in silico approaches.
  • Measured potency against the NNMT enzyme activity and cytotoxicity in OSCC cells (SCC-4).
  • Assessed the effect on cellular energy metabolism in SCC-4 and other cancer cells using oxygen consumption.
  • Conducted immunoblotting to analyze NNMT expression in various cell lines.
  • NNMT is overexpressed in SCC-4 and DOK cells but not in MCF-7 cells.
  • The NNMT inhibitors demonstrated effective inhibition of NNMT enzyme activity and showed cytotoxic effects on SCC-4 cells.
  • Inhibitors reduced mitochondrial oxygen consumption in SCC-4 and DOK cells without affecting MCF-7 cells.
  • NNMT inhibitors are proposed to influence mitochondrial activity without directly inhibiting the electron transport chain.

Cite This Study

Maloney et al. (2026) studied this question.

synapsesocial.com/papers/69c37b93b34aaaeb1a67e234https://doi.org/10.3390/ph19030516
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