# From fragments to follow-ups: rapid hit expansion by making use of EU-OPENSCREEN resources

## TL;DR

This paper describes a method to quickly expand initial drug hits into more effective compounds using resources from EU-OPENSCREEN.

## Contribution

The study introduces a streamlined approach for hit expansion using the EFSL-96 fragment library and the EU-OPENSCREEN infrastructure.

## Key findings

- A 96-member subset of the European Fragment Screening Library (EFSL-96) was defined and validated.
- Hit rates of 31% and 18% were achieved for endothiapepsin and NS2B–NS3 Zika protease targets.
- Two follow-up binders for each target were identified using the European Chemical Biology Library.

## Abstract

Quite frequently, it is the progression of initial crystallographic fragment screening hits into more potent binders to their target, which constitutes the major bottleneck in many academic compound or drug development projects. While high quality starting points are critical to the success of a drug development project, it is equally important to have accessible pathways for further compound development. Here, we present two crystallographic fragment screening campaigns using a 96 fragment sub-selection of the European Fragment Screening Library (EFSL) provided by EU-OPENSCREEN. The two campaigns against the targets endothiapepsin and the NS2B–NS3 Zika protease, yielded hit rates of 31% and 18%, respectively. Further, we present how within the framework of the EU-OPENSCREEN European Research Infrastructure Consortium (ERIC) fast identification of follow-up compounds can be realized. With just one round of testing related compounds from the European Chemical Biology Library, two follow-up binders for each of the two targets could be identified proving the feasibility of this approach.

Definition and validation of EFSL-96, a 96-membered subset of the European Fragment Screening Library. Hits and follow-up binder identification for endothiapepsin and NS2B–NS3 Zika protease.