Preface for the special issue on analysis of drug or drug targets by molecular imaging

To increase the chance of a successful outcome in clinic and in the development of innovative drugs,researchers aim to provide more compre hensive information about the disease and drugs to adapt treatment decisions according to an individual disease's mo-lecular characteristics.It is thus increasingly desirable to illuminate fund amental molecular pathways of the drug and its targets inside organisms in a non-invasive manner.Technologies developed in molecular imaging assist in visualizing,characterizing,and quanti-fying targets of interest at the molecular level within intact living organisms.This special issue of Joumal of Pharmaceutical Analysis is therefore dedicated to highlighting current progresses made in molecular imaging towards various drugs,important or promising drug targets,and their interactions,as well as to providing a forum for sharing new methods reported recently for the efficient phar-maceutical analysis.

A targeted covalent inhibitor of p97 with proteome-wide selectivity

A resurging interest in targeted covalent inhibitors(TCIs)focus on compounds capable of irreversibly reacting with nucleophilic amino acids in a druggable target.p97 is an emerging protein target for cancer therapy,viral infections and neurodegenerative diseases.Extensive efforts were devoted to the development of p97 inhibitors.The most promising inhibitor of p97 was in phase 1 clinical trials,but failed due to the off-target-induced toxicity,suggesting the selective inhibitors of p97 are highly needed.We report herein a new type of TCIs(i.e.,FL-18)that showed proteome-wide selectivity towards p97.Equipped with a Michael acceptor and a basic imidazole,FL-18 showed potent inhibition towards U87 MG tumor cells,and in proteome-wide profiling,selectively modified endogenous p97 as confirmed by in situ fluorescence scanning,label-free quantitative proteomics and functional validations.FL-18 selectively modified cysteine residues located within the D2 ATP site of p97.This covalent labeling of cysteine residue in p97 was verified by LC-MS/MS-based site-mapping and site-directed mutagenesis.Further structure-activity relationship(SAR)studies with FL-18 analogs were established.Collectively,FL-18 is the first known small-molecule TCI capable of covalent engagement of p97 with proteome-wide selectivity,thus providing a promising scaffold for cancer therapy.

A reversible microarray immobilization strategy based on thiol-quinone reaction

Microarray technology has been widely applied in biomedical research.The key to microarray study is to develop efficient immobilization method.In this study,we designed a new reversible microarray immobilization method based on thiol-quinone reaction.A quinone-functionalized slide was fabricated through H_(2)O_(2)treatment of dopamine-coated slides.Various thiol-containing molecules can be anchored onto the quinone-functionalized slides via thioether linker,which could be cleaved under H_(2)O_(2) treatment to regenerate quinone groups on the surface.The highly versatile approach can be widely used for immobilization of various thiol-containing molecules.