Fragment-based lead discovery
Encyclopedia
Fragment-based lead discovery (FBLD) is a method used for finding lead compound
s as part of the drug discovery
process. It is based on identifying small chemical fragments, which may bind only weakly to the biological target
, and then growing them or combining them to produce a lead with a higher affinity. FBLD can be compared with high-throughput screening
(HTS). In HTS, libraries with up to millions of compounds, with molecular weights of around 500 Da
, are screened, and nanomolar binding affinities are sought. In contrast, in the early phase of FBLD, libraries with a few thousand compounds with molecular weights of around 200 Da may be screened, and millimolar affinities can be considered useful.
Lead compound
A lead compound in drug discovery is a chemical compound that has pharmacological or biological activity and whose chemical structure is used as a starting point for chemical modifications in order to improve potency, selectivity, or pharmacokinetic parameters.Lead compounds are often found in...
s as part of the drug discovery
Drug discovery
In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are discovered or designed.In the past most drugs have been discovered either by identifying the active ingredient from traditional remedies or by serendipitous discovery...
process. It is based on identifying small chemical fragments, which may bind only weakly to the biological target
Biological target
A biological target is a biopolymer such as a protein or nucleic acid whose activity can be modified by an external stimulus. The definition is context-dependent and can refer to the biological target of a pharmacologically active drug compound, or the receptor target of a hormone . The...
, and then growing them or combining them to produce a lead with a higher affinity. FBLD can be compared with high-throughput screening
High-throughput screening
High-throughput screening is a method for scientific experimentation especially used in drug discovery and relevant to the fields of biology and chemistry. Using robotics, data processing and control software, liquid handling devices, and sensitive detectors, High-Throughput Screening allows a...
(HTS). In HTS, libraries with up to millions of compounds, with molecular weights of around 500 Da
Atomic mass unit
The unified atomic mass unit or dalton is a unit that is used for indicating mass on an atomic or molecular scale. It is defined as one twelfth of the rest mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state, and has a value of...
, are screened, and nanomolar binding affinities are sought. In contrast, in the early phase of FBLD, libraries with a few thousand compounds with molecular weights of around 200 Da may be screened, and millimolar affinities can be considered useful.