title: Kinetic target-guided synthesis in drug discovery and chemical biology: a comprehensive facts and figures survey.
abstract: For the last 15 years, kinetic target-guided syntheses, including in situ click chemistry, have been used as alternative methods to find ligands to therapeutically relevant proteins. In this review, a comprehensive survey of biological targets used in kinetic target-guided synthesis covers historical and recent examples. The chemical reactions employed and practical aspects, including controls, library sizes and product detection, are presented. A particular focus is on the reagents and warhead selection and design with a critical overview of the challenges encountered. As protein supply remains a key success factor, it appears that increased efforts should be taken toward miniaturization in order to expand the scope of this strategy and qualify it as a fully fledged drug discovery tool.
authors.affiliation: Inserm, Institut Pasteur de Lille, U1177 Drugs & Molecules for Living Systems, Université de Lille, F-59000 Lille, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Bosc
authors.affiliation: Inserm, Institut Pasteur de Lille, U1177 Drugs & Molecules for Living Systems, Université de Lille, F-59000 Lille, France.
authors.forename: Jouda
authors.initials: J
authors.lastname: Jakhlal
authors.affiliation: Inserm, Institut Pasteur de Lille, U1177 Drugs & Molecules for Living Systems, Université de Lille, F-59000 Lille, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Deprez
authors.affiliation: Inserm, Institut Pasteur de Lille, U1177 Drugs & Molecules for Living Systems, Université de Lille, F-59000 Lille, France.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Deprez-Poulain
mesh_terms: D057930:Click Chemistry; D055808:Drug Discovery; D006801:Humans; D007700:Kinetics; D008024:Ligands; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis* / Q000737:chemistry; D011506:Proteins; D011795:Surveys and Questionnaires
chemical_list: D008024:Ligands; D004364:Pharmaceutical Preparations; D011506:Proteins