Cell permeable affinity- and activity-based probes.
Chemical biology has a significant role to play in the discovery and validation of new therapeutic targets. Activity- and affinity-based probes have demonstrated considerable promise in the drug discovery setting as they provide a chemoproteomic means to confirm and quantify target engagement and selectivity of small molecule drug candidates. Many of these technologies have been developed using cell lysate (through the use of resin-immobilized enzyme inhibitors for example), but this does not represent the biology of an intact cell. This review highlights recent advances made in the design and application of cell-permeable probes that report on target activity and drug-target occupancy in living cells, thus providing a means to decipher molecular pharmacology and pathology in a more physiologically relevant manner.
WorldWide Medicinal Chemistry, Pfizer, 610 Main Street, Cambridge, MA 02139, USA.
Lyn H
LH
Jones
D001665:Binding Sites; D002463:Cell Membrane Permeability; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D057054:Molecular Imaging; D015335:Molecular Probes / Q000032:analysis* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism
D015335:Molecular Probes; D054852:Small Molecule Libraries