A simple method for predicting serum protein binding of compounds from IC50 shift analysis for in vitro assays

Bioorganic and Medicinal Chemistry Letters

Volumn 14, Issue 9, 2004, Pages 2309-2312

  Rusnak, David W ^a   Lai, Zhihong ^a   Lansing, Timothy J ^a   Rhodes, Nelson ^a   Gilmer, Tona M ^a   Copeland, Robert A ^a  

^a GLAXOSMITHKLINE   (United States)

Author keywords

Plasma binding; Serum protein binding

Indexed keywords

PHOSPHOTRANSFERASE INHIBITOR; PLASMA PROTEIN;

ANALYTIC METHOD; ARTICLE; CELL LINE; ENZYME ACTIVITY; ENZYME INHIBITION; IC 50; PLASMA PROTEIN BINDING; PREDICTION; PROTEIN BINDING;

BLOOD PROTEINS; PROTEIN BINDING;

EID: 1842639528     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2004.01.103     Document Type: Article

References (5)

1. Oravoca J., Bohs B., Linder W. Drug-protein binding studies. New trends in analytical and experimental methodology. J. Chromatogr. B. 677:1996;1-28.
2. Copeland R.A. Determination of serum protein binding affinity of inhibitors from analysis of concentration-response plots in biochemical activity assays. J. Pharm. Sci. 89:2000;1000-1007.
3. ′ as a function of [P] would deviate from linearity.
4. Case records of the Massachusetts General Hospital. Normal references values. New England J. Med. 314:1986;39-49.
5. Compound binding to human serum proteins was studied by equilibrium dialysis at a fixed concentration of 2 μg/mL. The average molecular weight of the compounds studied here was ∼500 Da. Thus the average molar concentration of compound in the equilibrium dialysis measurements was 4 μM.