Supplementary Figure 1 Supplementary Figure 1. Screen for small-molecule compounds modulating luciferase activity. Claudin-4 reporter cells were seeded in 96-well plates, treated with 10 μM TSA, apicidin, scriptaid, or SAHA for 24 h, and luciferase activity in cell lysates was measured. Relative luciferase activity is the ratio of luciferase activity in the compound-treated cells to that in the DMSO-treated cells. 1

Supplementary Figure 2. Dose-dependent effects of the claudin-4 modulator candidates on luciferase activity. Claudin-4 reporter cells were treated with daunorubicin, halcinonide, chetomin, fluvastatin, strophanthidin, trichostatin A (TSA), SAHA, scriptaid, sapintoxin D, nabumetone, or thiabendazole at the indicated concentrations for 24 h. Relative luciferase activity is the ratio of luciferase activity in the compound-treated cells to that in the DMSO-treated cells. The data are means ± S.D. (n = 3). Supplementary Figure 2 2

Supplementary Figure 3. Effects of claudin-4 modulator candidates on cell viability. Claudin-4 reporter cells were seeded in 96-well plates and treated with T-2 toxin, HT-2 toxin, homoharringtonine, 17-AAG, or geldanamycin (10 μM each). After 24 h, the LDH release was determined. Tween20 (0.2%) was used as a positive control. The data are means ± S.D. (n = 3). Supplementary Figure 3 3

4 Supplementary Figure 4 Supplementary Figure 4 Effects of the claudin-4 modulator candidates (T-2 toxin, HT-2 toxin, Ochratoxin, Homoharringtonine, 17-AAG, and Geldanamycin) on claudin-4 mRNA expression. Claudin-4 reporter cells were treated with T-2 toxin (10  M), HT-2 toxin (10  M), Ochratoxin (10  M), Homoharringtonine (10  M), 17-AAG (10  M), or Geldanamycin (10  M) for 24 h, and claudin-4 mRNA expression was analyzed by qPCR. Claudin-4 mRNA level was normalized to the GAPDH level. The data are means ± S.D. (n = 3).