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Updated: Sep 28, 2026

A Rapid and Quantitative Fluorimetric Method for Protein-Targeting Small Molecule Drug Screening
Published on: October 16, 2015
Competition binding experiments for rapidly ranking lead molecules for their binding affinity to human serum albumin
Claudio Dalvit1, Maria Flocco, Brian J Stockman
1Chemistry Department, Pharmacia, Viale Pasteur 10, Nerviano (MI), 20014, Italy. claudio.dalvit@pharmacia.com
Abstract:
Many lead molecules that have high affinity for a therapeutic target in vitro exhibit a reduced efficacy in vivo. Drug binding to human serum albumin is a major contributor to this reduction in potency, and many drug discovery programs expand significant resources preparing compounds that have decreased albumin binding. As rational and structure-based approaches have already been demonstrated to design compounds that have reduced affinity for albumin, the ability to rapidly and accurately assess protein binding will be valuable in lead optimization. This review will summarize some of the NMR-based efforts towards developing universal, rapid, accurate, and site-specific assays for estimating protein binding.
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