title: Small-molecule affinity chromatography coupled mass spectrometry for drug target deconvolution.
abstract: BACKGROUND
  Current drug discovery organizations have renewed interest in phenotypic/function based screening for the identification of novel small-molecule drug candidates. Phenotypic screening faces the challenge of deconvoluting the identity of molecular targets of small-molecules through which they exert their biological effect. The identity of the target is crucial for understanding the mechanism of drug action, rational drug design, interpretation of any toxicological findings and patient stratification. Several methods are available to deconvolute the targets of small-molecules.
  
  
  OBJECTIVE
  This review describes successful examples, limitations and advances of drug target deconvolution using small-molecule affinity chromatography coupled mass spectrometry based methods. A brief discussion of other target deconvolution methods is also presented for comparative appreciation of mass spectrometry based methods.
  
  
  CONCLUSIONS
  The use of small-molecule affinity chromatography coupled mass spectrometry based methods is gaining popularity as a technique for target identification. Mass spectrometry based methods provide fast, reliable and high-content information on the target. They can be used with relatively intact biological systems to develop a system-wide understanding of the drug-target interaction.
authors.affiliation: Integrative Biology, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA +1 317 651 1539 ; +1 317 433 8767 ; saxena_chaitanya@lilly.com.
authors.forename: Chaitanya
authors.initials: C
authors.lastname: Saxena
authors.forename: Richard E
authors.initials: RE
authors.lastname: Higgs
authors.forename: Eugene
authors.initials: E
authors.lastname: Zhen
authors.forename: John E
authors.initials: JE
authors.lastname: Hale