In conjunction with analytical DSF, we identified a variety of known ligands as new TPST1 and TPST2 inhibitors, including the promiscuous protein kinase inhibitor rottlerin and a family of oxindole-based RAF (rapidly accelerated fibrosarcoma) kinase inhibitors from the Published Kinase Inhibitor Set (PKIS). Here, TPST1 is linked to fibrosarcoma.