Montagner, Diego and Velasco-Torrijos, Trinidad and Beirne, Darren and Dalla Via, Martina (2022) Metal-Tyrosine Kinase Inhibitors: Targeted Metal-drug Conjugates. -. (Submitted)

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Abstract

Tyrosine Kinases are enzymes that catalyse the phosphorylation of the tyrosine residues of their substrates and activate downstream pathways involved in cellular proliferation. Their overexpression/hyper-activity is implicated in numerous different cancerous cell lines. Small molecule Tyrosine Kinase Inhibitors (TKi’s), such as Imatinib, Erlotinib and Sunitinib have been developed as targeted anti-cancer chemotherapeutics but, at the moment, their clinical usage is hindered due to acquired and innate resistance and/or dose limiting side effects. Recently, Metal-Tyrosine Kinase Inhibitor conjugates have become a promising field to overtake these drawbacks since the TKi’s show potential to improve selectivity and pharmacological properties of metal-based drugs, overcoming the resistance associated with current TKi’s. Metal-Tyrosine Kinase Inhibitor conjugates further find applications is several biological fields as dual-modal activity drugs, pro-drug systems and selective metal theragnostics. In this review, advancements over the past decade in the field of metal based-TKi conjugates are discussed and insights are provided to successfully develop metal – TKi conjugates. Three main TK targets are discussed, EGFR (Epidermal Growth Factor Receptor), PDGFR (Platelet Derived Growth Factor Receptor) VEGFR (Vascular Endothelial Growth Factor Receptor). Future perspectives and applications of this promising research area are also outlined.

Item Type:	Article
Additional Information:	This is the submitted version of the article.
Keywords:	Small molecule Tyrosine Kinase Inhibitors (TKi’s); targeted anti-cancer chemotherapeutics; Metal-Tyrosine Kinase Inhibitors; Targeted Metal-drug Conjugates;
Academic Unit:	Faculty of Science and Engineering > Chemistry
Item ID:	15475
Depositing User:	Diego Montagner
Date Deposited:	14 Feb 2022 14:42
Journal or Publication Title:	-
Refereed:	Yes
Funders:	Irish Research Council
URI:
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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