Fig. 6: CTCB compounds are highly specific and have a very fast time-to-kill compared with all available clinical anti-HAT drugs.

a CTCB-405 shows no significant inhibition of human PFK. Enzyme activity was measured using an aldolase/TIM linked assay at 25 °C. Enzyme activities of T. brucei PFK, hPFK-M and hPFK-P were measured as described in Supplementary Methods 2.3 (Supplementary Fig. 4 shows similar result for titrations of CTCB-508, and CTCB-470 against hPFK-L). Experiments were carried out in duplicate. Data are presented as mean values ± standard deviation. Highest concentration of CTCB-405 = 100 μM. Source data are provided as a Source Data File. b Kill time of CTCB-405 compared with existing HAT drugs in the clinic. The cell viability assay was used to study the effect of a fixed concentration of suramin (11 µM), fexinidazole (11 µM), SCYX-7158 (11 µM) and CTCB-405 (4 µM). Over 99% of trypanosomes were killed in under 30 min compared with much slower killing rates for the other drugs. The points on the graph for CTCB-405 were determined from two independent biological replicate experiments with each time point measured twice (using duplicate technical replicates). The ESD for each point on the graph is between 0.7 and 1.4%. For drugs in clinical use each point on the graph is the average of two technical replicates from one experiment (with a maximum difference of 7.8% for any of the points). Source data are provided as a Source Data File.