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Updated: Jun 25, 2025

Characterization of the Effects of Migrastatic Inhibitors on 3D Tumor Spheroid Invasion by High-resolution Confocal Microscopy
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The Selective SIRT3 Inhibitor 3-TYP Represses Primary Myeloma Growth by Reducing c-Myc Stability

Yindi Zeng1,2, Yaxin Zhang1,2, Zeyu Cui2

  • 1Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu, China.

Chemical Research in Toxicology
|May 30, 2024
PubMed

Insights

Researchers identified 3-TYP, a novel SIRT3 inhibitor, as a potential treatment for multiple myeloma. This compound effectively targets c-Myc, reducing tumor growth and offering new hope for patients with this incurable blood cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Multiple myeloma is an incurable hematological cancer with frequent relapse.
  • Current chemotherapy improves quality of life but does not offer a cure.
  • There is an urgent need for novel, highly active, and specific inhibitors for targeted therapy.

Purpose of the Study:

  • To identify novel inhibitors for multiple myeloma treatment.
  • To investigate the mechanism of action of identified compounds.
  • To evaluate the therapeutic potential of identified inhibitors in preclinical models.

Main Methods:

  • Screening of a histone modification compound library to identify potential inhibitors.
  • In vitro assessment of cytotoxicity and DNA damage induction in myeloma cells.
  • In vivo xenograft tumor studies to evaluate tumor growth inhibition.
  • Analysis of c-Myc protein stability and phosphorylation levels.

Main Results:

  • The SIRT3 inhibitor 3-TYP (3-(1H-1,2,3-triazol-4-yl) pyridine) was identified.
  • 3-TYP demonstrated high cytotoxicity and induced DNA damage in myeloma cells.
  • 3-TYP inhibited primary myeloma growth in xenograft models.
  • Compound 3-TYP reduced c-Myc protein stability by decreasing c-Myc Ser62 phosphorylation.

Conclusions:

  • 3-TYP is identified as a novel inhibitor of c-Myc.
  • The compound exhibits potent anti-myeloma activity through c-Myc targeting.
  • 3-TYP represents a potential chemotherapeutic agent for multiple myeloma treatment.

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