A novel method using nuclear magnetic resonance for plasma protein binding assessment in drug discovery programs

被引：15

作者：

Gallo, Mariana ^{[1
]}

Matteucci, Sara ^{[2
]}

Alaimo, Nadine ^{[2
]}

Pitti, Erica ^{[2
]}

Orsale, Maria, V ^{[1
]}

Summa, Vincenzo ^{[1
]}

Cicero, Daniel O. ^{[1
,2
]}

Monteagudo, Edith ^{[1
]}

机构：

[1] IRBM Sci Pk SpA, Via Pontina Km 30-600, I-00071 Rome, Italy

[2] Univ Roma Tor Vergata, Dipartimento Sci & Tecnol Chim, Via Ric Sci, I-00133 Rome, Italy

来源：

JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS | 2019年 / 167卷

关键词：

Plasma protein binding; NMR; Protein-ligand interaction; Drug discovery; Screening; CLINICAL PHARMACOKINETICS; ALPHA-1-ACID GLYCOPROTEIN; ZIDOVUDINE; VERAPAMIL; KINETICS;

D O I：

10.1016/j.jpba.2019.01.049

中图分类号：

O65 [分析化学];

学科分类号：

070302 ; 081704 ;

摘要：

A new methodology based on Nuclear Magnetic Resonance (NMR) was developed to determine plasma protein binding (PPB) of drug candidates in drug discovery programs. A strong correlation was found between the attenuation of NMR signals of diverse drugs in the presence of different plasma concentrations and their fraction bound (f(b)) reported in the literature. Based on these results, a protocol for a rapid calculation of fb of small molecules was established. The advantage of using plasma instead of purified recombinant proteins and the possibility of pool analysis to increase throughput were also evaluated. This novel methodology proved to be very versatile, cost-effective, fast and suitable for automation. As a plus, it contemporarily provides a quality check and solubility of the compound. (C) 2019 The Authors. Published by Elsevier B.V.

引用

页码：21 / 29

页数：9

共 37 条

[1] Quantification of molecules in 1H-NMR metabolomics with formate as a concentration standard [J].

Ando, Itiro ;

Hirose, Takuo ;

Nemoto, Tadashi ;

Totsune, Kazuhito ;

Imai, Yutaka ;

Takeuchi, Kazuhisa ;

Fujiwara, Masako .

JOURNAL OF TOXICOLOGICAL SCIENCES, 2010, 35 (02) :253-256

[2]

ANDREASEN F, 1973, ACTA PHARMACOL TOX, V32, P417

[3]

Becker W, 2018, CHEMPHYSCHEM, V19, P895, DOI 10.1002/cphc.201701253

[4] Plasma Protein Binding: From Discovery to Development [J].

Bohnert, Tonika ;

Gan, Liang-Shang .

JOURNAL OF PHARMACEUTICAL SCIENCES, 2013, 102 (09) :2953-2994

[5] Bioanalysis for plasma protein binding studies in drug discovery and drug development: views and recommendations of the European Bioanalysis Forum [J].

Buscher, Brigitte ;

Laakso, Sirpa ;

Mascher, Hermann ;

Pusecker, Klaus ;

Doig, Mira ;

Dillen, Lieve ;

Wagner-Redeker, Winfried ;

Pfeifer, Thomas ;

Delrat, Pascal ;

Timmerman, Philip .

BIOANALYSIS, 2014, 6 (05) :673-682

[6] CLINICAL PHARMACOKINETICS OF IMIPRAMINE AND DESIPRAMINE IN ALCOHOLICS AND NORMAL VOLUNTEERS [J].

CIRAULO, DA ;

BARNHILL, JG ;

JAFFE, JH .

CLINICAL PHARMACOLOGY & THERAPEUTICS, 1988, 43 (05) :509-518

[7] BINDING OF PARACETAMOL TO PLASMA-PROTEINS OF MAN AND PIG [J].

GAZZARD, BG ;

FORDHUTC.AW ;

SMITH, MJH ;

WILLIAMS, R .

JOURNAL OF PHARMACY AND PHARMACOLOGY, 1973, 25 (12) :964-967

[8] BINDING OF 5-FLUORO-L-TRYPTOPHAN TO HUMAN-SERUM ALBUMIN [J].

GERIG, JT ;

KLINKENBORG, JC .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1980, 102 (12) :4267-4268

[9] Plasma Protein Binding in Drug Discovery and Development [J].

Howard, Monique L. ;

Hill, John J. ;

Galluppi, Gerald R. ;

McLean, Matthew A. .

COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING, 2010, 13 (02) :170-187

[10]

Huang ZQ, 2013, CURR DRUG METAB, V14, P226

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