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Current perspectives in fragment-based lead discovery (FBLD).
- Source :
-
Essays in biochemistry [Essays Biochem] 2017 Nov 08; Vol. 61 (5), pp. 453-464. Date of Electronic Publication: 2017 Nov 08 (Print Publication: 2017). - Publication Year :
- 2017
-
Abstract
- It is over 20 years since the first fragment-based discovery projects were disclosed. The methods are now mature for most 'conventional' targets in drug discovery such as enzymes (kinases and proteases) but there has also been growing success on more challenging targets, such as disruption of protein-protein interactions. The main application is to identify tractable chemical startpoints that non-covalently modulate the activity of a biological molecule. In this essay, we overview current practice in the methods and discuss how they have had an impact in lead discovery - generating a large number of fragment-derived compounds that are in clinical trials and two medicines treating patients. In addition, we discuss some of the more recent applications of the methods in chemical biology - providing chemical tools to investigate biological molecules, mechanisms and systems.<br /> (© 2017 The Author(s).)
- Subjects :
- Biphenyl Compounds chemical synthesis
Biphenyl Compounds therapeutic use
Clinical Trials as Topic
Drug Discovery methods
Humans
Indoles therapeutic use
Molecular Docking Simulation
Neoplasm Proteins genetics
Neoplasm Proteins metabolism
Neoplasms genetics
Neoplasms metabolism
Neoplasms pathology
Nitrophenols chemical synthesis
Nitrophenols therapeutic use
Piperazines chemical synthesis
Piperazines therapeutic use
Protein Binding
Proto-Oncogene Proteins B-raf antagonists & inhibitors
Proto-Oncogene Proteins B-raf genetics
Proto-Oncogene Proteins B-raf metabolism
Proto-Oncogene Proteins p21(ras) antagonists & inhibitors
Proto-Oncogene Proteins p21(ras) genetics
Proto-Oncogene Proteins p21(ras) metabolism
Small Molecule Libraries therapeutic use
Structure-Activity Relationship
Sulfonamides chemical synthesis
Sulfonamides therapeutic use
Thermodynamics
Vemurafenib
Combinatorial Chemistry Techniques
Drug Design
Neoplasm Proteins antagonists & inhibitors
Neoplasms drug therapy
Small Molecule Libraries chemical synthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1744-1358
- Volume :
- 61
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Essays in biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 29118093
- Full Text :
- https://doi.org/10.1042/EBC20170028