WZH-21 is a selective and orally active dual HDAC1/2 inhibitor, exhibiting an IC50 of 34 nM for HDAC1 and 41 nM for HDAC2. It inhibits the growth of HCT116 and SW480 cells with IC50 values of 0.524 μM and 1.063 μM, respectively. WZH-21 suppresses proliferation and migration of various colorectal cancer cells and induces apoptosis (apoptosis). It is applicable in cancer research, including studies on colorectal cancer.

HDAC1:34 nM

ZWZH-21 effectively inhibits the growth of A549, MCF-7, and HepG2 cells, with IC 50 values of 1.66 μM, 2.445 μM, and 1.551 μM respectively. It suppresses the temperature-induced degradation of HDAC1/2 in HCT116 cells at concentrations of 0.4-1.6 μM over 48 hours. This compound also induces the degradation of HDAC1 and HDAC2 proteins and the formation of Ac-H3 and histone H4 in a concentration-dependent manner within HCT116 cells. ZWZH-21 reduces the colony-forming ability of HCT116 and SW480 cells and inhibits their migration while inducing apoptosis when applied at 0.4-2 μM for 48 hours. Additionally, ZWZH-21 triggers G1 phase arrest in HCT116 and SW480 cells under similar conditions.

ZWZH-21 (2000 mg/kg, single oral dose) has demonstrated good safety in mice. In addition, ZWZH-21 (30-120 mg/kg, via gavage, administered daily for 14 days) effectively inhibited tumor growth in mice implanted with HCT116 human colon cancer xenografts.