Identification of intracellular targets of small molecular weight chemical compounds using affinity chromatography.
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.
Guiffant
Damien
D
CNRS, Molecules and Therapeutic Targets Laboratory, Station Biologique, Roscoff, France.
Tribouillard
Déborah
D
Gug
Fabienne
F
Galons
Hervé
H
Meijer
Laurent
L
Blondel
Marc
M
Bach
Stéphane
S
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*
D001704:Biopolymers; D004364:Pharmaceutical Preparations