**4. Conclusions**

In this study, screening of a comparatively small fragment library by two different screening methods has allowed identification of several compounds that interact with and inhibit *Tb*CK, a genetically validated drug target against African sleeping sickness. Some of the in‐ hibitory fragments were also selectively trypanocidal, considering these are relatively sim‐ ple molecules with no optimization, finding low µΜ inhibitors is very encouraging. Moreover some of the morphological phenotypes of these trypanocidal compounds include cell-cycle arrests similar to those observed for the *Tb*CK conditional knockout grown under permissive conditions.

This study highlights that if faced with a drug target that is problematic to screen, prior ther‐ mal shift analysis could significantly triage the number of compounds to be screened, there‐ by significantly increasing the potential to identify lead compounds. This approach obviously has the limitation that potential inhibitors could be missed if they do not signifi‐ cantly alter the Tm of the protein.

Future follow up work with *Tb*CK will include expanding the structure activity relationship of our most promising hits identified by this study. Their trypanocidal mode of action will be investigated by undertaking various *in vivo* biochemical phenotyping experiments to as‐ certain if they are inhibiting *Tb*CK, thus causing a lack of *de novo* PC synthesis, known to be essential for the parasite.

The ultimate goal is to identify new easy to make, affordable, easy to administer, drugs in the fight against African sleeping sickness and other closely related protozoan transmitted Third World diseases.
