title: Design Principles for Fragment Libraries: Maximizing the Value of Learnings from Pharma Fragment-Based Drug Discovery (FBDD) Programs for Use in Academia.
abstract: Fragment-based drug discovery (FBDD) is well suited for discovering both drug leads and chemical probes of protein function; it can cover broad swaths of chemical space and allows the use of creative chemistry. FBDD is widely implemented for lead discovery in industry but is sometimes used less systematically in academia. Design principles and implementation approaches for fragment libraries are continually evolving, and the lack of up-to-date guidance may prevent more effective application of FBDD in academia. This Perspective explores many of the theoretical, practical, and strategic considerations that occur within FBDD programs, including the optimal size, complexity, physicochemical profile, and shape profile of fragments in FBDD libraries, as well as compound storage, evaluation, and screening technologies. This compilation of industry experience in FBDD will hopefully be useful for those pursuing FBDD in academia.
authors.affiliation: Research Centre for Natural Sciences, Hungarian Academy of Sciences , Magyar tudósok körútja 2, H-1117, Budapest, Hungary.
authors.forename: György M
authors.initials: GM
authors.lastname: Keserű
authors.affiliation: Carmot Therapeutics, Inc. 409 Illinois Street, San Francisco, California 94158, United States.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Erlanson
authors.affiliation: Research Centre for Natural Sciences, Hungarian Academy of Sciences , Magyar tudósok körútja 2, H-1117, Budapest, Hungary.
authors.forename: György G
authors.initials: GG
authors.lastname: Ferenczy
authors.affiliation: Medicines Research Centre, GlaxoSmithKline , Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Hann
authors.affiliation: Astex Pharmaceuticals , 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, U.K.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Murray
authors.affiliation: Medicines Research Centre, GlaxoSmithKline , Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Pickett
mesh_terms: D000818:Animals; D064447:Checkpoint Kinase 2 / Q000037:antagonists & inhibitors; D015195:Drug Design; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology*; D014361:Trypsin Inhibitors / Q000737:chemistry / Q000494:pharmacology
chemical_list: D019428:HIV Integrase Inhibitors; D018841:HSP90 Heat-Shock Proteins; D061965:Matrix Metalloproteinase Inhibitors; D047428:Protein Kinase Inhibitors; D054852:Small Molecule Libraries; D014361:Trypsin Inhibitors; D064447:Checkpoint Kinase 2; D048308:Mitogen-Activated Protein Kinase 14; D053508:Matrix Metalloproteinase 12