Intrinsically Fluorescent Anti-Cancer Drugs

SIMPLE SUMMARY: Cancer is one of the biggest causes of death world-wide. The development of anti-cancer drugs is important in combatting this disease. As good as these drugs appear to be, they do suffer from problems such as side-effects and disease resistance. We surmise that an improved understanding of drug-target and drug non-target interactions is important in addressing these issues. Here we review the use of a spectroscopic method called fluorescence to provide this needed information on target and non-target interactions. Fortunately, some of the drugs used pre-clinically or in the clinic are intrinsically fluorescent and thus can be used as spectroscopic probes of their own environment. ABSTRACT: At present, about one-third of the total protein targets in the pharmaceutical research sector are kinase-based. While kinases have been attractive targets to combat many diseases, including cancer, selective kinase inhibition has been challenging, because of the high degree of structural homology in the active site where many kinase inhibitors bind. Despite efficacy as cancer drugs, kinase inhibitors can exhibit limited target specificity and rationalizing their target profiles in the context of precise molecular mechanisms or rearrangements is a major challenge for the field. Spectroscopic approaches such as infrared, Raman, NMR and fluorescence have the potential to provide significant insights into drug-target and drug-non-target interactions because of sensitivity to molecular environment. This review places a spotlight on the significance of fluorescence for extracting information related to structural properties, discovery of hidden conformers in solution and in target-bound state, binding properties (e.g., location of binding sites, hydrogen-bonding, hydrophobicity), kinetics as well as dynamics of kinase inhibitors. It is concluded that the information gleaned from an understanding of the intrinsic fluorescence from these classes of drugs may aid in the development of future drugs with improved side-effects and less disease resistance.