A growing threat from drug resistance means there is an urgent need for new therapeutics and novel mechanisms of action for antimalarial drug discovery. Epigenetic mechanisms, including histone methylation, are vital throughout the Plasmodium lifecycle, and could provide exciting new targets. BIX-01294 and a series of diaminoquinazolines are putative Plasmodium histone lysine methyltransferase inhibitors, with exciting antimalarial properties, although robust evidence for their molecular targets is lacking. To this end, a well-developed SAR for this series allowed for the development of small-molecule photo-crosslinkable probes to investigate the targets. These probes effectively label Plasmodium falciparum lysates and show similarities with the target profiles of BIX-01294 and the diaminoquinazoline series. Initial pull-down proteomics experiments with two different probes identified 45 common proteins from different classes, many of which are essential, highlighting the suitability of the developed probes as valuable tools for target identification in Plasmodium falciparum.