Based on Enamine's REAL Space, hundreds of individually substituted and tens of thousands of larger, leadlike follow-up compounds are available for each fragment. Overall, the 96fragment core library gives access to over 14 million follow-up compounds in Enamine's REAL Space. A correspondingly higher number of follow-up compounds is available for the 1098 fragment clusters. To prove its usefulness, this fragment library was used for a crystallographic fragment screening on Mycobacterium smegmatis thioredoxin reductase (Msm-TrxR). Due to a high sequence identity, this enzyme serves as a model for its homologue in Mycobacterium tuberculosis (Mtb-TrxR). Effective inhibition of the validated drug target Mtb-TrxR would allow the development of new drugs for the treatment of tuberculosis, which is still one of the deadliest infectious diseases, with around 1.5 million deaths annually. With its substrate thioredoxin (Trx), the TrxR is essential for thiol redox homeostasis and maintaining infection. To date we report the identification of 24 bound fragments as a result of a preliminary analysis of the crystallographic fragment screening.