Ezrin Inhibitors in Cancer Treatment

OVERVIEW

Researchers at Georgetown University discovered groundbreaking compounds and their pharmaceutically acceptable salts that can revolutionize the field of pharmaceutical chemistry and therapeutics. The patented compounds and their pharmaceutically acceptable salts are meticulously designed to inhibit the ezrin protein within cells, unlocking a new era of therapeutic possibilities. With high ezrin expression linked to lung metastasis and poor cancer survival rates, this innovation aims at the underlying molecular events driving metastasis, offering a potential lifeline for patients with dire prognoses. One particular focus of this invention lies in osteosarcoma (OS), the primary bone cancer affecting children and adolescents. Given its complex etiology and heterogeneous histology, understanding OS pathogenesis has posed a significant challenge. However, by targeting ezrin, a critical protein involved in OS metastasis and various other tumor types, the innovative compounds aim to disrupt the early stages of pulmonary metastases and potentially revolutionize the treatment landscape. Moreover, the applications of this invention extend beyond OS, encompassing other pediatric cancers such as rhabdomyosarcoma.

BACKGROUND

Ezrin is a protein that plays a significant role in cell signaling, cytoskeletal organization, and cell motility. Ezrin is a key factor in metastases. Ezrin is often overexpressed or dysregulated in cancer cells, contributing to tumor progression, metastasis, and invasion. When ezrin is inhibited, either through specific inhibitors or by interfering with its activity, it can lead to several effects that hinder the growth of cancer cells. Inhibition of ezrin can disrupt cellular processes involved in cancer cell proliferation, survival, and migration. It can interfere with signaling pathways that promote tumor growth and metastasis, ultimately reducing the aggressiveness of cancer cells. Overall, inhibiting ezrin protein in cells, especially cancer cells, presents a promising avenue for therapeutic intervention by restraining tumor growth, metastasis, and invasion.

Benefit

• Ezrin inhibitors offer unrivaled therapeutic potential, targeting and modulating ezrin activity for treating cancer, inflammation, and metastasis.
• High selectivity and specificity in ezrin protein inhibition, reducing off-target effects and enabling targeted therapies with enhanced patient safety and tolerability.
• Robust manufacturing methods for ezrin inhibitors, ensuring reproducibility and scalability.
• Compounds of the invention can be administered intravenously, intravenously intramuscularly, intraperitoneally, and orally.

Market Application

• Promising method to hinder cancer progression, suppress metastasis, and improve patient outcomes and survival rates, making it a viable treatment option for metastatic OS.
• Broad applications in veterinary and human medicine, effectively treating or preventing conditions related to uncontrolled cell growth.

Publications

• U.S. Patent No. 9,522,908
• Small molecule inhibitors of ezrin inhibit the invasive phenotype of osteosarcoma cells. Bulut G. et al., Oncogene, 2012 Jan 19;31(3):269-81.
• The ezrin metastatic phenotype is associated with the initiation of protein translation. Briggs et al., Neoplasia, 2012 Apr;14(4):297-310.
• Ezrin Binds to DEAD-Box RNA Helicase DDX3 and Regulates Its Function and Protein Level. Mol Cell Biol. 2015 Sep;35(18):3145-62. doi: 10.1128/MCB.00332-15.
  
• Ezrin Inhibition Up-regulates Stress Response Gene Expression. J Biol Chem. 2016 Jun 17;291(25):13257-70. doi: 10.1074/jbc.M116.718189.