We explored differential protein expression (DEPs) during sublethal exposures of HKMT inhibitors (BIX-01294 = 10uM (B), Chaetocin = 20uM (C)) in log-phase (growth; TY) and encystation (differentiation; EC) at 8 and 24 hours relative to DMSO controls (D). In total, 18,527 peptides from 1,981 proteins in log-phase, and 19,852 peptides from 2,097 proteins were analysed in encysting cultures. In total, 56 proteins were up- and 36 down-regulated in log-phase trophozoites and 32 up- and 12 down during encystation upon BIX-01294-treatment relative to the DMSO controls. Following Chaetocin-treatment, 195 proteins were up- and 121 down-regulated in log-phase trophozoites, and 63 up- and 12 down during encystation. We have presented results by cell-phase given positive correlations were driven by culture condition and not between either Chaetocin or BIX-01294 inhibitor).