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.

Gallo, M., Matteucci, S., Alaimo, N., Pitti, E., Orsale, M.v., Summa, V., et al. (2019). A novel method using nuclear magnetic resonance for plasma protein binding assessment in drug discovery programs. JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, 167, 21-29 [10.1016/j.jpba.2019.01.049].

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

Gallo M.;Alaimo N.;Cicero D. O.
;
2019-01-01

Abstract

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.
2019
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10 - BIOCHIMICA
English
Drug discovery; NMR; Plasma protein binding; Protein-ligand interaction; Screening; Blood Proteins; Drug Discovery; Drug Evaluation, Preclinical; Humans; In Vitro Techniques; Pharmaceutical Preparations; Protein Binding; Recombinant Proteins; Serum Albumin, Human; Small Molecule Libraries; Nuclear Magnetic Resonance, Biomolecular
Gallo, M., Matteucci, S., Alaimo, N., Pitti, E., Orsale, M.v., Summa, V., et al. (2019). A novel method using nuclear magnetic resonance for plasma protein binding assessment in drug discovery programs. JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, 167, 21-29 [10.1016/j.jpba.2019.01.049].
Gallo, M; Matteucci, S; Alaimo, N; Pitti, E; Orsale, Mv; Summa, V; Cicero, Do; Monteagudo, E
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/227097
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