title: De novo fragment design: a medicinal chemistry approach to fragment-based lead generation.
abstract: The use of fragments with low binding affinity for their targets as starting points has received much attention recently. Screening of fragment libraries has been the most common method to find attractive starting points. Herein, we describe a unique, alternative approach to generating fragment leads. A binding model was developed and a set of guidelines were then selected to use this model to design fragments, enabling our discovery of a novel fragment with high LE.
authors.affiliation: Hoffmann-La Roche Inc, Pharma Research & Early Development, 340 Kingsland Street, Nutley, New Jersey 07110, United States. franciscotalamas@gmail.com
authors.forename: Francisco X
authors.initials: FX
authors.lastname: Talamas
authors.forename: Gloria
authors.initials: G
authors.lastname: Ao-Ieong
authors.forename: Ken A
authors.initials: KA
authors.lastname: Brameld
authors.forename: Elbert
authors.initials: E
authors.lastname: Chin
authors.forename: Javier
authors.initials: J
authors.lastname: de Vicente
authors.forename: James P
authors.initials: JP
authors.lastname: Dunn
authors.forename: Manjiri
authors.initials: M
authors.lastname: Ghate
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Giannetti
authors.forename: Seth F
authors.initials: SF
authors.lastname: Harris
authors.forename: Sharada S
authors.initials: SS
authors.lastname: Labadie
authors.forename: Vincent
authors.initials: V
authors.lastname: Leveque
authors.forename: Jim
authors.initials: J
authors.lastname: Li
authors.forename: Alfred S-T
authors.initials: AS
authors.lastname: Lui
authors.forename: Kristen L
authors.initials: KL
authors.lastname: McCaleb
authors.forename: Isabel
authors.initials: I
authors.lastname: Nájera
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Schoenfeld
authors.forename: Beihan
authors.initials: B
authors.lastname: Wang
authors.forename: April
authors.initials: A
authors.lastname: Wong
mesh_terms: D002626:Chemistry, Pharmaceutical; D015195:Drug Design; D008958:Models, Molecular