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Updated: Oct 12, 2025

Development of a Backbone Cyclic Peptide Library as Potential Antiparasitic Therapeutics Using Microwave Irradiation
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Discovery and Development of Cyclic Peptide Inhibitors of CIB1

Victoria A Haberman1,2, Steven R Fleming1,2, Tina M Leisner2,3

  • 1Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, United States.

ACS Medicinal Chemistry Letters
|November 19, 2021
PubMed

Insights

Researchers developed UNC10245131, a novel cyclic peptide inhibitor targeting Calcium and integrin binding protein 1 (CIB1) in triple-negative breast cancer (TNBC). This inhibitor shows improved stability and potency, offering a potential new therapeutic strategy for TNBC.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Cancer Research

Background:

  • Calcium and integrin binding protein 1 (CIB1) is implicated in triple-negative breast cancer (TNBC) survival and proliferation.
  • CIB1's interaction with PAK1 suggests it as a potential therapeutic target for TNBC.
  • Previous CIB1 inhibitors faced challenges with potency and stability.

Purpose of the Study:

  • To discover novel cyclic peptide inhibitors of CIB1 with enhanced biophysical properties and cellular activity.
  • To overcome limitations of existing CIB1 inhibitors for potential therapeutic applications in TNBC.

Main Methods:

  • Utilized mRNA display technology for the discovery of cyclic peptide inhibitors.
  • Characterized the affinity, selectivity, permeability, and stability of identified inhibitors.
  • Assessed the cytotoxicity and impact on downstream signaling of the lead compound.

Main Results:

  • Identified UNC10245131, a cyclic peptide inhibitor with low nanomolar affinity and high selectivity for CIB1.
  • UNC10245131 demonstrated improved permeability and stability compared to previous linear peptide inhibitors.
  • UNC10245131 exhibited no cytotoxicity and did not affect downstream signaling pathways.

Conclusions:

  • UNC10245131 is a potent CIB1 ligand with favorable drug-like properties.
  • This cyclic peptide inhibitor holds promise for further investigation into CIB1's role in TNBC.
  • UNC10245131 could serve as a valuable tool for studying CIB1-associated biological processes.

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