ST13 is an ortho-hydroxyaniline compound that functions as a selective, slow-binding inhibitor of HDAC1 and HDAC2, exhibiting IC50 values of 23 nM and 49 nM, respectively. It shows relatively weaker inhibition for HDAC3 (IC50= 4.30 μM) and HDAC6 (IC50 > 10 μM). The mechanism of induced binding by ST13 occurs through a two-step process: initially, a rapid formation of the collision complex (EI) between the enzyme and inhibitor occurs, followed by a gradual conversion to a stable complex (E*I). Additionally, ST13 can induce apoptosis in cancer cells and is applicable in research involving melanoma and triple-negative breast cancer.

HDAC1:23 nM

ST13 exhibits time-dependent antiproliferative effects in cancer cell lines over 72-120 hours. In MV-3 cells, the EC50 value decreases from 2.77 µM at 72 hours to 0.311 µM at 120 hours, and in MDA-MB-231 cells, it reduces from 4.87 µM at 72 hours to 0.087 µM at 120 hours. At a concentration of 10 µM for 48 hours, ST13 significantly induces apoptosis in MDA-MB-231 cells. It also increases acetylated histone H3 levels in MV-3 cells when used at 5 μM for 24-72 hours. Further, ST13 demonstrates inhibitory effects on HDACs in MV-3 cells, MDA-MB-231 cells, non-tumor HEK293 cells, and hematological MM.1S cells after an 18-hour treatment, with EC50 values of 0.311 μM, 0.577 μM, 0.333 μM, and 0.637 μM respectively. Additionally, ST17, the photo-activated prodrug of ST13, at concentrations of 0.040 µM and 0.072 µM for 10 minutes, effectively inhibits HDAC1/HDAC2 under UV irradiation.