Supramolecular alleviation of cardiotoxicity of a small-molecule kinase inhibitor.

Abstract

Small-molecule kinase inhibitors (SMKIs) have been widely used in the treatment of a variety of cancers due to their clinically demonstrated efficacy. However, the use of some SMKIs, such as sorafenib (SO), has been plagued by their cardiotoxicity that has been frequently observed in treated patients. Herein we report that the encapsulation of SO by a synthetic receptor cucurbit[7]uril (CB[7]) alleviated the inherent cardiotoxicity of SO, as demonstrated in an in vivo zebrafish model. Moreover, the anti-cancer activity of SO was well preserved, upon its encapsulation by CB[7], as demonstrated by both in vitro and in vivo cancer/angiogenesis models. This discovery may provide new insights into a novel supramolecular formulation of SMKIs for the management of their side-effects.

• Authors: Xue Yang, Qiaoxian Huang, David Bardelang, Chunming Wang, Simon M Y Lee, Ruibing Wang
• Journal: Organic & biomolecular chemistry (Org Biomol Chem) Vol. 15 Issue 38 Pg. 8046-8053 (Oct 04 2017) ISSN: 1477-0539 [Electronic] England
• PMID: 28795750 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Bridged-Ring Compounds
• Imidazoles
• Macromolecular Substances
• Phenylurea Compounds
• cucurbit(7)uril
• Niacinamide
• Sorafenib

Topics

• Animals
• Antineoplastic Agents (adverse effects, chemistry, pharmacology)
• Bridged-Ring Compounds (chemistry)
• Cardiotoxicity
• Cell Line, Tumor
• Cell Survival (drug effects)
• Embryo, Nonmammalian (drug effects)
• Humans
• Imidazoles (chemistry)
• Macromolecular Substances
• Magnetic Resonance Spectroscopy
• Molecular Structure
• Neovascularization, Physiologic (drug effects)
• Niacinamide (adverse effects, analogs & derivatives, chemistry)
• Phenylurea Compounds (adverse effects, chemistry)
• Sorafenib
• Zebrafish