Tyrosine kinase inhibitor (TKI) coordinated to cobalt reduces adverse effects

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According to a new study published in the journal Angewandte Chemie [Applied Chemistry], International Edition, researchers from the Institute of Organic Chemistry at the University of Vienna and the Institute for Cancer Research at the Medical University of Vienna in Vienna, Austria, have developed a new tyrosine kinase inhibitor (TKI) that is only activated when it is distributed to malignant tissue, thereby minimizing damage to healthy cells and reducing adverse effects experienced by patients.

The drug is coordinated to cobalt(3) which leads to initial drug inactivity. When the drug reaches the malignant tissue, the cobalt(3) is converted to cobalt(2) due to hypoxia in the malignant tissue, which in turn releases the active TKI. Researchers hope that this method for reducing adverse effects in patients taking TKIs will be studied in clinical trials in the future.

Although the adverse events of TKIs like sunitinib and erlotinib are typically somewhat manageable, more severe adverse events often lead to dose reductions and discontinuation of therapy. Side effects may include nausea, fatigue, diarrhea. Rash is specific to erlotinib and occurs in the majority of patients taking the drug.

Tyrosine kinase inhibitor (TKI) coordinated to cobalt reduces adverse effects
Researchers have developed a new TKI that is only activated when distributed to malignant tissue.

An interdisciplinary team of researchers from the University of Vienna (Institute of Inorganic Chemistry) and the Medical University of Vienna (Institute for Cancer Research) has successfully developed a new strategy for reducing the often serious side effects of an important class of modern anticancer drugs (tyrosine kinase inhibitors).

The novel drug is supposed to restrict its activity with high selectivity to the malignant tumour. The occurrence of severe side effects and the development of resistance are two of the biggest problems facing modern cancer therapy. Even the latest, highly targeted cancer drugs such as the tyrosine kinase inhibitors TarcevaÒ or SutentÒ are affected by these problems, which can ultimately lead to treatment having to be stopped.

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