Norleual

Product Name:Norleual

CAS No:334994-34-2

Purity:95%

Molar Mass:774.95

Chemical Formula:C41H58N8O7

Storage:Store at -20 degrees Celsius

Sequence:{Nle}-Y-{Leu-(CH2-NH2)}-HPF

Target:HGF

Application:Norleual is a modified angiotensin IV peptide that acts as an antagonist of the hepatocyte growth factor (HGF) and its receptor, c-Met. By inhibiting the HGF/c-Met pathway, Norleual has been explored for its potential in cancer research, particularly in limiting tumor growth and metastasis. This peptide is also of interest in regenerative medicine and tissue repair, as the HGF pathway plays a critical role in cellular proliferation, migration, and angiogenesis. Norleual??s modulation of HGF activity could provide therapeutic benefits in conditions where this signaling is overactive, such as in cancer or fibrosis.

Current Research:

Norleual, an analog of angiotensin IV (Ang IV), is a potent inhibitor of hepatocyte growth factor (HGF) and its receptor c-Met, exhibiting an IC₅₀ of 3 pM. It also functions as an antagonist of the AT₄ receptor and demonstrates significant antiangiogenic properties.

Structural Characteristics

Norleual is a modified hexapeptide with the sequence Nle-Tyr-Leu-ψ-(CH₂-NH₂)-His-Pro-Phe. This structure includes a reduced peptide bond (ψ) between Leu and His, enhancing its stability and inhibitory activity.

Mechanism of Action

By binding directly to HGF, Norleual disrupts its dimerization, a process essential for c-Met activation. This inhibition effectively blocks HGF-induced cellular responses, including proliferation and invasion, particularly in cancer cells.

Biological Activities

Anti-Proliferative Effects: Norleual inhibits HGF-induced proliferation of MDCK cells in vitro, demonstrating its potential to suppress tumor growth.

Anti-Invasive Properties: It reduces HGF-stimulated invasion of cancer cells, indicating its role in preventing metastasis.

Antiangiogenic Activity: Norleual exhibits potent antiangiogenic effects, further contributing to its anticancer potential.

Research Applications

Due to its multifaceted inhibitory effects, Norleual is utilized in research to explore therapeutic strategies against cancers driven by HGF/c-Met signaling. Its ability to antagonize the AT₄ receptor also makes it a valuable tool in studying the renin-angiotensin system and related pathologies.

Conclusion

Norleual stands as a significant compound in biomedical research, offering insights into the modulation of HGF/c-Met signaling and its implications in cancer therapy. Its dual role as an HGF/c-Met inhibitor and AT₄ receptor antagonist underscores its potential in developing treatments for various diseases.

Reference:

Yamamoto, B. J., Elias, P. D., Masino, J. A., Hudson, B. D., McCoy, A. T., Anderson, Z. J., … & Harding, J. W. (2010). The angiotensin IV analog Nle-Tyr-Leu-ψ-(CH2-NH2) 3-4-His-Pro-Phe (Norleual) can act as a hepatocyte growth factor/c-Met inhibitor. Journal of Pharmacology and Experimental Therapeutics, 333(1), 161-173.