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Updated: Aug 9, 2025

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Screening method toward ClbP-specific inhibitors.

Tao Zhou1,2, Takayuki Ando3, Akihiro Kudo3

  • 1Adenoprevent Co., Ltd., Shizuoka, 422-8526, Japan.

Genes and Environment : the Official Journal of the Japanese Environmental Mutagen Society
|February 16, 2023
PubMed
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Researchers developed a new screening system to find inhibitors for ClbP, an enzyme crucial for activating colibactin, a genotoxin linked to colorectal cancer (CRC). This method could aid in developing new CRC prevention strategies.

Area of Science:

  • Microbiology
  • Biochemistry
  • Cancer Research

Background:

  • Colibactin, a genotoxin from Enterobacteriaceae, is associated with increased colorectal cancer (CRC) risk.
  • The peptidase ClbP is essential for activating colibactin, and its inhibition could prevent CRC.
  • Developing ClbP-specific inhibitors offers a potential strategy for CRC prophylaxis.

Purpose of the Study:

  • To establish an efficient screening system for identifying ClbP-specific inhibitors.
  • To facilitate the development of novel prophylactic agents against CRC.

Main Methods:

  • A sequential screening approach combining a rapid probe assay and an accurate LC-MS assay was employed.
  • The probe assay detects ClbP activity by measuring fluorophore release.
  • LC-MS quantifies N-myristoyl-D-asparagine, a byproduct of colibactin maturation, for precise inhibition assessment.
Keywords:
ClbPColibactinFluorescentInhibitorProbeScreening

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Main Results:

  • A library of 67,965 compounds was screened using the established method.
  • One compound exhibiting moderate inhibitory activity against ClbP was identified.

Conclusions:

  • A reliable and efficient screening method for ClbP inhibitors has been successfully established.
  • This method is valuable for discovering potential prophylactic agents for colorectal cancer.