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Updated: Apr 14, 2026

Monitoring Functionality and Morphology of Vasculature Recruited by Factors Secreted by Fast-growing Tumor-generating Cells
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Monitoring Functionality and Morphology of Vasculature Recruited by Factors Secreted by Fast-growing Tumor-generating Cells

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New inhibitors of angiogenesis with antitumor activity in vivo

Nagore I Marín-Ramos1, Dulce Alonso, Silvia Ortega-Gutiérrez

  • 1‡CEI Campus Moncloa, UCM-UPM and CSIC, E-28040 Madrid, Spain.

Journal of Medicinal Chemistry
|April 24, 2015
PubMed

Insights

A novel compound effectively inhibits tumor angiogenesis by blocking the MAPK pathway and reducing blood vessel formation in breast cancer models. This compound shows promise for developing new anti-cancer therapies with minimal toxicity.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Solid tumor growth relies on angiogenesis, the formation of new blood vessels.
  • Inhibiting proangiogenic signaling, especially under hypoxic tumor conditions, remains a critical unmet medical need.
  • Tumor hypoxia stimulates proangiogenic factors, driving tumor progression.

Purpose of the Study:

  • To investigate a novel anti-angiogenic compound (compound 22) for its efficacy in inhibiting proangiogenic signaling in breast cancer cells under hypoxic conditions.
  • To elucidate the molecular mechanisms underlying the anti-angiogenic effects of compound 22.
  • To evaluate the in vivo anti-tumor activity and safety profile of compound 22 in a preclinical breast cancer model.

Main Methods:

  • In vitro studies using breast cancer cell lines under hypoxic conditions.
  • Assessment of MAPK pathway activity, cellular migration, and gene expression related to angiogenesis.
  • Hypoxia-inducible factor 1-alpha (HIF-1α) knockdown experiments.
  • In vivo efficacy and toxicity studies using a breast cancer xenograft mouse model.

Main Results:

  • Compound 22 effectively inhibited proangiogenic signaling in breast cancer cells under hypoxia.
  • The compound blocked the MAPK pathway, impaired cellular migration, and modulated angiogenesis-related genes.
  • Compound 22 demonstrated significant tumor growth reduction (46-55%) in 38% of treated animals in a xenograft model, with no observed toxicity.
  • A notable decrease in tumor blood vessel density was observed in responding tumors, supporting the anti-angiogenic mechanism.

Conclusions:

  • Compound 22 is a potent inhibitor of tumor angiogenesis, acting via HIF-1α and the MAPK pathway.
  • The compound exhibits promising preclinical anti-tumor efficacy and a favorable safety profile.
  • These findings support the development of compound 22 as a potential therapeutic agent for cancer treatment, possibly in combination therapies.

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