A comprehensive screening method for investigating the potential binding targets of doxorubicin based on protein microarray.

ABSTRACT

With the development of precision therapy, pharmacological research pays more and more attention to seek and confirm the target of drugs in order to understand the mechanism of drug action and reduce side effects. Screening candidate proteins can be effectively used to predict potential drug targets and toxicity. Therefore, a high-throughput drug-binding protein screening method based on protein microarray which contains over 21,000 human proteins was introduced in this investigation. Doxorubicin, a classical chemotherapeutic agent widely used in clinical treatment, was taken as a drug example in our protein screening study. Through microarray and bioinformatics analysis, more potential targets were found with different binding affinity to doxorubicin, and HRAS stands out as a critical protein from candidate proteins. In addition, the results revealed that the formation of the HRAS-RAF complex is promoted by doxorubicin. It is our expectation that the outcomes could benefit to understand the various effect of the doxorubicin and push the protein microarray screening to apply in the comprehensive pharmacological and toxicological investigation of other drugs.