Classifying shape coverage in fragment libraries using a fingerprinting approach.

Fragment screening is one approach to hit identification for early stage drug discovery projects. Like any screening library, diversity is needed in fragment libraries. This includes coverage of shape and electrostatic space, as well as chemotype diversity.

Strategies for small molecule library design.

Compilation of an appropriate set of compounds is essential for the success of a small molecule screen. When very little is known about the target and when no or few ligands have been identified, the screening file is often made as diverse as possible. When structural information on the target or target family is available or ligands of the target are known, it is more efficient to apply a ligand- or target-focused bias, so as to predominantly screen compounds that can be expected to modulate the target.

How large does a compound screening collection need to be?

Increasingly, chemical libraries are being produced which are focused on a biological target or group of related targets, rather than simply being constructed in a combinatorial fashion. A screening collection compiled from such libraries will contain multiple analogues of a number of discrete series of compounds. The question arises as to how many analogues are necessary to represent each series in order to ensure that an active series will be identified.