Rapid on-line profiling of estrogen receptor binding metabolites of tamoxifen.
Here we present a high-resolution screening (HRS) methodology for postcolumn on-line profiling of metabolites with affinity for the estrogen receptor alpha (ERalpha). Tamoxifen, which is metabolized into multiple metabolites, was used as the model compound. Most of the 14 metabolites detected exhibited affinity for the ERalpha. The HRS methodology shows great potential for metabolite bio-affinity profiling and application in drug discovery and development.
Kool
Jeroen
J
Leiden Amsterdam Center for Drug Research/Division of Molecular Toxicology, Department of Chemistry and Pharmacochemistry, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.
Ramautar
Rawi
R
van Liempd
Sebastiaan M
SM
Beckman
Joran
J
de Kanter
Frans J J
FJ
Meerman
John H N
JH
Schenk
Tim
T
Irth
Hubertus
H
Commandeur
Jan N M
JN
Vermeulen
Nico P E
NP
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation; D004965:Estrogen Antagonists / Q000378:metabolism* / Q000493:pharmacokinetics; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D066298:In Vitro Techniques; D008024:Ligands; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization; D013552:Swine; D013629:Tamoxifen / Q000378:metabolism* / Q000493:pharmacokinetics
D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D008024:Ligands; D013629:Tamoxifen