Year: 2026
Type: article
Abstract: Fragment-based inhibitor design is an established and widely used approach in drug discovery pipelines. Despite several examples of drugs originating from this approach, the identification of fragments still suffers from issues with solubility, reactivity, cost and worldwide accessibility. Here, we design a low-cost minimal fragment library (LoCoFrag100) for crystallographic screening, with an average cLogP of 0.03 (median 0.23) and an average of £20/g for each compound, facilitating assembly in any laboratory. Formatted in a 10 × 10 matrix to minimize Tanimoto similarity in the 20 cocktails, we demonstrate its applicability on three structurally distinct enzymes involved in microbial cell wall synthesis. Hit rates range from 1 to 6% among these enzymes, with three fragments suggesting avenues for inhibitor exploration. Impact Statement LoCoFrag100 is a low-cost, easily accessible fragment library that enables rapid survey of target ligandability in any laboratory, providing evidence to prioritise targets for follow-up research.
Source: FEBS Letters
Language: English
Subfield: Computational Theory and Mathematics
Field: Computer Science
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $3,980
Awards: Decoding the biosynthesis machinery and role in host-pathogen interactions of the streptococcal Group A Carbohydrate, G5486736228, G5776794654, G632655458, Decoding the biosynthesis machinery and role in host-pathogen interactions of the streptococcal Group A Carbohydrate, G6559006734, Genetic and chemical validation of sugar nucleotide biosynthesis as a target against Candida albicans, G8916790994
OpenAlex ID: W7124197821