Developments of mass spectrometry-based technologies for effective drug development linked with clinical proteomes. Issue 1 (February 2016)

• Record Type: Journal Article
• Authors: Nakayama, Noboru; Bando, Yasuhiko; Fukuda, Tetsuya; Kawamura, Takeshi; Nakamura, Haruhiko; Marko-Varga, György; Nishimura, Toshihide
• Is Part Of: Drug metabolism and pharmacokinetics. Volume 31:Issue 1(2016)
• Page Start: 3
• Page End: 11
• Publication Date: 2016-02
• Subjects: Mass spectrometry -- LC-MS/MS/MS -- SRM -- MALDI -- Clinical specimens -- MS-based clinical proteomics -- Nanopore optical interferometry (nPOI) -- H/D exchange -- AP-SMALDI -- Protein–protein interaction (PPI); Drugs -- Metabolism -- Periodicals; Pharmacokinetics -- Periodicals; 615.7
• DOI: 10.1016/j.dmpk.2015.11.008
• Languages: English
• ISSNs: 1347-4367

Abstract

Abstract: A strong demand in drug discovery and development today is to overcome "Big Gaps" encountered by differences in species and races, to accelerate effective developments in cost and time, and to meet medical needs. Moreover, drugs of various types have emerged which cover middle-size molecules and polymers rather than conventional small molecules. Upon those challenges, mass spectrometry (MS)-based technologies, which will be described in this paper, will play an increasingly important role, among which the liquid chromatography–tandem mass spectrometry (LC/MS/MS) platform will be powerful as rapid and molecule-based analysis more than ever. nano Pore Optical Interferometry ( n POI) newly introduced can detect even weak interactions in protein–protein and protein–compound, and can be connected directly to LC/MS/MS for identification of binding molecular species, which will be quite useful for affinity ranking and high-throughput interaction screening. Imaging MS provides the molecular information and spatial distribution of targeted molecules within a tissue specimen. MS-based clinical proteomics utilizing clinical specimens and empowered by advanced bioinformatics can attain both key protein–protein interaction (PPI) networks with major protein players responsible for functional mechanisms of a disease subtype. An integration of those MS-based technologies will deliver a seamless platform of drug development from molecules identified in human clinical specimens.