Development of a novel near-infrared fluorescent theranostic combretastain A-4 analogue, YK-5-252, to target triple negative breast cancer
| Autor: | Yali Kong, John Han, Kongwen Li, Shujie Hou, Jacqueline Smith, Milton L. Brown, Jake Cui |
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| Rok vydání: | 2017 |
| Předmět: |
Fluorophore
Disulfide Linkage Proton Magnetic Resonance Spectroscopy Clinical Biochemistry Pharmaceutical Science Triple Negative Breast Neoplasms Pharmacology 010402 general chemistry 01 natural sciences Biochemistry Mass Spectrometry Theranostic Nanomedicine chemistry.chemical_compound Cell Line Tumor Stilbenes Drug Discovery Humans Benzopyrans Molecular Biology Triple-negative breast cancer Cell Proliferation Combretastatin 010405 organic chemistry Organic Chemistry Glutathione Prodrug Flow Cytometry Small molecule Tubulin Modulators 0104 chemical sciences chemistry Toxicity Molecular Medicine |
| Zdroj: | Bioorganic & Medicinal Chemistry. 25:2226-2233 |
| ISSN: | 0968-0896 |
| Popis: | The treatment of triple negative breast cancer (TNBC) is a significant challenge to cancer research. The lack of hormone receptors limits the treatment options available to patients with this diagnosis, forcing them to endure prolonged radiation and chemotherapy. Anti-angiogenesis is a chemotherapeutic strategy that targets the vasculature of tumors. Combretastatin A-4 (CA-4) is a well-known vasculature-disrupting agent, which has been shown to effectively kill a variety of cancers through inhibition of tubulin polymerization. Due to its toxicity, small molecule analogues of CA-4 have been sought out. We have designed a novel dual action CA-4 prodrug, YK-5-252, which releases the drug through a disulfide bond cleavage mechanism and contains a near-infrared (NIR) fluorophore, which allows fluorescence monitoring of cleavage. This disulfide linkage causes CA-4 to become effective only when released by glutathione (GSH) reducing the toxicity of the drug while simultaneously releasing the NIR fluorophore. Therefore the prodrug, YK-5-252, represents a novel CA-4 analogue which has reduced toxicity and can be used for theranostics imaging. |
| Databáze: | OpenAIRE |
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