Fragment-based hit identification: thinking in 3D

•Current fragment libraries possess limited three-dimensional shape.•Principal moments of inertia are a useful way to rapidly assess molecular shape.•Bespoke synthesis is beneficial in generating diverse fragment libraries.•Pre-competitive networks are valuable but are challenging to operate successfully. The identification of high-quality hits during the early phases of drug discovery is essential if projects are to have a realistic chance of progressing into clinical development and delivering marketed drugs. As the pharmaceutical industry goes through unprecedented change, there are increasing opportunities to collaborate via pre-competitive networks to marshal multifunctional resources and knowledge to drive impactful, innovative science. The 3D Fragment Consortium is developing fragment-screening libraries with enhanced 3D characteristics and evaluating their effect on the quality of fragment-based hit identification (FBHI) projects.