title: Identification of intracellular targets of small molecular weight chemical compounds using affinity chromatography.
abstract: Efforts to characterize small molecular weight chemical inhibitors of pharmacological interest tend to identify molecules with high efficiency and selectivity, to meet the two criteria required for the clinical development of a drug: efficacy and harmlessness. Drug candidates are expected to inhibit efficiently the target they have been optimized against (for example, a particular type of protein kinase). These hits are also designed to not interfere (or as little as possible) with the activity of other cellular enzymes/proteins to reduce undesired side effects. Here we discuss the use of immobilized drugs as affinity chromatography matrices to purify and identify their bona fide intracellular targets. This method not only allows the systematic investigation of the selectivity of pharmacological compounds but also the anticipation of their putative adverse effects.
authors.affiliation: CNRS, Molecules and Therapeutic Targets Laboratory, Station Biologique, Roscoff, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Guiffant
authors.forename: Déborah
authors.initials: D
authors.lastname: Tribouillard
authors.forename: Fabienne
authors.initials: F
authors.lastname: Gug
authors.forename: Hervé
authors.initials: H
authors.lastname: Galons
authors.forename: Laurent
authors.initials: L
authors.lastname: Meijer
authors.forename: Marc
authors.initials: M
authors.lastname: Blondel
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bach
mesh_terms: D001704:Biopolymers / Q000032:analysis* / Q000737:chemistry*; D002846:Chromatography, Affinity / Q000379:methods*; D015195:Drug Design; D008832:Microchemistry / Q000379:methods*; D008970:Molecular Weight; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D013347:Subcellular Fractions / Q000737:chemistry*
chemical_list: D001704:Biopolymers; D004364:Pharmaceutical Preparations