title: Monitoring drug-serum protein interactions for early ADME prediction through Surface Plasmon Resonance technology.
abstract: Many molecules fail to reach the market due to poor pharmacokinetic (PK) properties, rendering the potential drug virtually unavailable for the primary target despite efficient administration to the body. PK properties of endogenous and exogenous compounds in mammals are dependent, among other factors, on their ability to interact with serum proteins. The extent of binding can greatly influence their ADME (adsorption, distribution, metabolism and execration) profile. Reliable and cost-effective bioavailability studies, early in the drug discovery process, can lead to an improvement of the success rate for compounds entering clinical trials. Optical biosensors based on surface plasmon resonance (SPR) detection emerged as an efficient approach to obtain large amounts of information about the binding of small molecules to serum proteins. Simple, automated and fast assays provide a good throughput, versatility and highly informative data output, rendering the methodology particularly suited for early screening. The ability to provide basic information on PK can be easily coupled to structure-activity relationship analysis. In this review, features of the technology and its employment for the study of serum protein-small molecule interactions are presented and discussed.
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy. Electronic address: edoardo.fabini2@unibo.it.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Fabini
authors.affiliation: Department of Chemistry - BMC, Uppsala University, SE-751 23 Uppsala, Sweden; Science for Life Laboratory, Uppsala University, SE-751 23 Uppsala, Sweden.
authors.forename: U Helena
authors.initials: UH
authors.lastname: Danielson
mesh_terms: D000818:Animals; D015374:Biosensing Techniques; D001798:Blood Proteins; D004347:Drug Interactions; D013329:Structure-Activity Relationship; D020349:Surface Plasmon Resonance
chemical_list: D001798:Blood Proteins
keywords: Alpha-1-acid glycoprotein; Drug–serum proteins interaction; Early ADME profiling; Human serum albumin; Optical biosensor; Surface plasmon resonance spectroscopy