title: The Impact of Chemical Probes in Drug Discovery: A Pharmaceutical Industry Perspective.
abstract: Chemical probes represent an important component of both academic and pharmaceutical drug discovery research. As a complement to prior reviews that have defined this scientific field, we aim to provide an industry perspective on the value of having high-quality chemical probes throughout the course of preclinical research. By studying examples from the internal Merck pipeline, we recognize that these probes require significant collaborative investment to realize their potential impact in clarifying the tractability and translation of a given therapeutic target. This perspective concludes with recommendations for chemical probe discovery aimed toward maximizing their potential to identify targets that result in the successful delivery of novel therapeutics.
authors.affiliation: Global Chemistry, Merck Research Laboratories, Mailstop 14-2, 740 Sumneytown Pike, West Point, PA 19486, USA. Electronic address: robert_garbaccio@merck.com.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Garbaccio
authors.affiliation: Global Chemistry, Merck Research Laboratories, Mailstop 14-2, 740 Sumneytown Pike, West Point, PA 19486, USA.
authors.forename: Emma R
authors.initials: ER
authors.lastname: Parmee
mesh_terms: D000818:Animals; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000737:chemistry / Q000494:pharmacology; D055808:Drug Discovery / Q000379:methods*; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D058990:Molecular Targeted Therapy; D014176:Protein Biosynthesis / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011506:Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D019428:HIV Integrase Inhibitors; D011506:Proteins; D043885:Receptor, Cannabinoid, CB2; D054852:Small Molecule Libraries; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D018819:Dipeptidyl Peptidase 4