TH-6 is a potent HDAC inhibitor with IC50s of 0.115, 0.135, 0.242, 0.138, 2.120 µM for HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, respectively. TH-6 inhibits cell migration and invasion. TH-6 induces apoptosis and cell cycle arrest at G2/M phase. TH-6 shows anti-tumor activity.
TH-6 (0-2 µM) shows antiproliferative activities in cancer cell lines and normal human lung cells[1].TH-6 (0-10 µM) inhibits tubulin polymerization with an IC50 value of 4.06 µM[1].TH-6 (0.03, 0.1, 0.3 1 µM; 24 h) increases the expression of Ac-α-Tubulin and AC-Histone H3 in HepG2 cells[1].TH-6 (7.5, 15, 30 nM) induces apoptosis and cell cycle arrest at G2/M phase[1].TH-6 (0-30 nM) decreases the MMP and increase ROS levels of HepG2 cells in a dose-dependent manner[1].TH-6 (7.5, 15, 30 nM; 48 h) inhibits cell migration and invasion in MDA-MB-231 cells and suppress the migration of HUVECs in a concentration-dependent manner[1].TH-6 shows favorable liver microsomal stability in vitro with t1/2 of 50.3 min[1].
TH-6 (10, 20 mg/kg; i.v.; daily for 21 days) shows anti-tumor activity in mouse[1].TH-6 (20 mg/kg) shows antivascular activity and a good cardiovascular safety profile in mouse[1].
References:
[1]. Zhu H, et al. Discovery of a Novel Vascular Disrupting Agent Inhibiting Tubulin Polymerization and HDACs with Potent Antitumor Effects. J Med Chem. 2022 Aug 4.