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Updated: Dec 20, 2025

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A H-REV107 Peptide Inhibits Tumor Growth and Interacts Directly with Oncogenic KRAS Mutants

Chang Woo Han1, Mi Suk Jeong2, Sung Chul Ha3

  • 1Department of Molecular Biology, College of Natural Sciences, Pusan National University, 2, Busandaehak-ro 63 beon-gil, Geumjeong-gu, Busan 46241, Korea.

Cancers
|June 4, 2020
PubMed

Insights

A novel peptide, H-REV107, directly interacts with Kirsten-RAS (KRAS) G12V mutations, inhibiting cancer cell proliferation. This discovery offers a new therapeutic strategy for KRAS-mutated cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Structural Biology

Background:

  • Kirsten-RAS (KRAS) mutations are prevalent in human cancers, posing significant therapeutic challenges due to low drug affinity.
  • Targeting KRAS mutations directly has been difficult, necessitating novel therapeutic approaches.

Purpose of the Study:

  • To investigate the interaction between the KRAS G12V mutant and the H-REV107 peptide.
  • To determine the structural basis of this interaction and its functional consequences for KRAS activity.
  • To evaluate the therapeutic potential of H-REV107 peptide in preclinical cancer models.

Main Methods:

  • Co-crystallization and X-ray diffraction to determine the structure of the KRAS G12V-H-REV107 complex.
  • Guanylate-binding protein (GDP) binding assays to assess KRAS inhibition.
  • Cell proliferation assays using pancreatic and colon cancer cell lines.
  • In vivo studies using xenotransplantation mouse models to evaluate tumor suppression.

Main Results:

  • The first crystal structure of the KRAS G12V-H-REV107 complex revealed a high-affinity interaction.
  • The H-REV107 peptide binds to the inactive, GDP-bound state of KRAS G12V, blocking its activation.
  • H-REV107 peptide demonstrated significant inhibition of pancreatic and colon cancer cell proliferation.
  • In vivo studies showed suppression of pancreatic tumor growth, reducing tumor volume and weight.

Conclusions:

  • The H-REV107 peptide acts as a direct inhibitor of KRAS G12V.
  • This interaction and resulting inhibition provide a foundation for developing novel therapeutics targeting KRAS-mutated cancers.
  • The findings facilitate the development of new drugs for patients with KRAS mutations.
Keywords:
H-REV107KRASoncogenic mutationtumor suppressor

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