Table 1.

Screening strategies

Screen	Description	Comments
High throughput	Large numbers of compounds analysed in a assay generally designed to run in plates of 384 wells and above	Large compound collections often run by big pharma but smaller compound banks can also be run in either pharma or academia which can help reduce costs. Companies also now trying to provide coverage across a wide chemical space using computer assisted analysis to reduce the numbers of compounds screened.
Focused screen	Compounds previously identified as hitting specific classes of targets (e.g. kinases) and compounds with similar structures	Can provide a cheaper avenue to finding a hit molecule but completely novel structures may not be discovered and there may be difficulties obtaining a patent position in a well-covered IP area
Fragment screen	Soak small compounds into crystals to obtain compounds with low mM activity which can then be used as building blocks for larger molecules	Can join selected fragments together to fit into the chemical space to increase potency. Requires a crystal structure to be available
Structural aided drug design	Use of crystal structures to help design molecules	Often used as an adjunct to other screening strategies within big pharma. In this case usually have docked a compound into the crystal and use this to help predict where modifications could be added to provide increased potency or selectivity
Virtual screen	Docking models: interogation of a virtual compound library with the X-ray structure of the protein or, if have a known ligand, as a base to develop further compounds on	Can provide the starting structures for a focused screen without the need to use expensive large library screens. Can also be used to look for novel patent space around existing compound structures
Physiological screen	A tissue-based approach fordetermination of the effects of a drug at the tissue rather than the cellular or subcellular level, for example, muscle contractility	Bespoke screens of lower throughput. Aim to more closely mimic the complexity of tissue rather than just looking at single readouts. May appeal to academic experts in disease area to screen smaller number of compounds to give a more disease relevant readout
NMR screen	Screen small compounds (fragments) by soaking into protein targets of known crystal or NMR structure to look for hits with low mM activity which can then be used as building blocks for larger molecules	Use of NMR as a structure determining tool

NMR, nuclear magnetic resonance.