Quantitative targeted proteomics for membrane transporter proteins: method and application.
Although global proteomics has shown promise for discovery of many new proteins, biomarkers, protein modifications, and polymorphisms, targeted proteomics is emerging in the proteomics research field as a complement to untargeted shotgun proteomics, particularly when a determined set of low-abundance functional proteins need to be measured. The function and expression of proteins related to drug absorption, distribution, metabolism, and excretion (ADME) such as cytochrome P450 enzymes and membrane transporters are of great interest in biopharmaceutical research. Since the variation in ADME-related protein expression is known to be a major complicating factor encountered during in vitro-in vivo and in vivo-in vivo extrapolations (IVIVE), the accurate quantification of the ADME proteins in complex biological systems becomes a fundamental element in establishing IVIVE for pharmacokinetic predictions. In this review, we provide an overview of relevant methodologies followed by a summary of recent applications encompassing mass spectrometry-based targeted quantifications of membrane transporters.
Pharmaceutical Candidate Optimization, Bristol-Myers Squibb, Princeton, New Jersey, 08543, USA.
Xi
X
Qiu
Hui
H
Zhang
Yurong
Y
Lai
D000818:Animals; D015195:Drug Design; D006801:Humans; D026901:Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism; D040901:Proteomics
D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations