title: Probing the probes: fitness factors for small molecule tools.
abstract: Chemical probes for interrogating biological processes are of considerable current interest. Cell permeable small molecule tools have a major role in facilitating the functional annotation of the human genome, understanding both physiological and pathological processes, and validating new molecular targets. To be valuable, chemical tools must satisfy necessary criteria and recent publications have suggested objective guidelines for what makes a useful chemical probe. Although recognizing that such guidelines may be valuable, we caution against overly restrictive rules that may stifle innovation in favor of a "fit-for-purpose" approach. Reviewing the literature and providing examples from the cancer field, we recommend a series of "fitness factors" to be considered when assessing chemical probes. We hope this will encourage innovative chemical biology research while minimizing the generation of poor quality and misleading biological data, thus increasing understanding of the particular biological area, to the benefit of basic research and drug discovery.
authors.affiliation: Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey, SM2 5NG, UK. paul.workman@icr.ac.uk
authors.forename: Paul
authors.initials: P
authors.lastname: Workman
authors.forename: Ian
authors.initials: I
authors.lastname: Collins
mesh_terms: D000818:Animals; D055808:Drug Discovery; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D015335:Molecular Probes / Q000737:chemistry* / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: D018841:HSP90 Heat-Shock Proteins; D015335:Molecular Probes; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors