GSK TCAKS dataset. Using whole-cell phenotypic assays, the GSK screening collection of 1.8 million compounds was screened against the three kinetoplastids most relevant to human disease, i.e. Leishmania donovani, Trypanosoma cruzi and Trypanosoma brucei. Secondary confirmatory and orthogonal intracellular anti-parasiticidal assays were conducted, and the potential for non-specific cytotoxicity determined with HepG2 assay. Hit compounds were chemically clustered and triaged for desirable physicochemical properties. Consequently, three anti-kinetoplastid chemical boxes of 222 compounds for Chagas-Box, 192 compounds for Leish-Box and 192 compounds for HAT-Box were assembled. The compound sets are provided as an open resource for future lead discovery programs, as well as to address important research questions.