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Fragment based discovery of a novel and selective PI3 kinase inhibitor
- Source :
- Bioorganicmedicinal chemistry letters. 21(21)
- Publication Year :
- 2011
-
Abstract
- We report the use of fragment screening and fragment based drug design to develop a PI3γ kinase fragment hit into a lead. Initial fragment hits were discovered by high concentration biochemical screening, followed by a round of virtual screening to identify additional ligand efficient fragments. These were developed into potent and ligand efficient lead compounds using structure guided fragment growing and merging strategies. This led to a potent, selective, and cell permeable PI3γ kinase inhibitor with good metabolic stability that was useful as a preclinical tool compound.
- Subjects :
- High concentration
Models, Molecular
Virtual screening
Cell Membrane Permeability
Fragment (computer graphics)
Kinase
Chemistry
Organic Chemistry
Clinical Biochemistry
Cell
Pharmaceutical Science
Metabolic stability
Ligand (biochemistry)
Biochemistry
Structure-Activity Relationship
medicine.anatomical_structure
Drug Stability
Drug Discovery
medicine
Molecular Medicine
Transferase
Molecular Biology
Protein Kinase Inhibitors
Phosphoinositide-3 Kinase Inhibitors
Subjects
Details
- ISSN :
- 14643405
- Volume :
- 21
- Issue :
- 21
- Database :
- OpenAIRE
- Journal :
- Bioorganicmedicinal chemistry letters
- Accession number :
- edsair.doi.dedup.....2f0b07a9952fa22cd4e7b662e31054ec