Apoptosis inducer 56

Apoptosis inducer56 is an apoptosis inducer that binds to DNA minor grooves, causing DNA damage through the upregulation of γH2AX and p-ATM expression. This compound induces endogenous apoptosis by causing S phase cell cycle arrest and increasing the p53 and Bax/Bcl-2 ratios, as well as promoting caspase-7 cleavage. It demonstrates higher selectivity for cancer cells compared to normal breast epithelial cells and is useful in breast cancer research.

Apoptosis inducer 56 (compound 1) selectively induces cytotoxicity in human breast cancer MCF-7 cells with an IC50 of 21.18 μM over 24 hours, without significant effects on non-malignant breast epithelial MCF-10A cells. At the concentration of 21.18 μM for 24 hours, it inhibits proliferation and colony formation of MCF-7 cells and induces S-phase cell cycle arrest. Additionally, it triggers apoptosis in 45% of MCF-7 cells and induces DNA damage-mediated apoptosis with 75.8% mitochondrial membrane depolarization. Apoptosis inducer 56 activates the DNA damage response (upregulating γ-H2AX, p-ATM, p-Chk2) and suppresses DNA repair (downregulating p-BRCA1) in MCF-7 cells. Furthermore, it induces mitochondria-dependent apoptosis by upregulating pro-apoptotic proteins, releasing cytochrome c, activating caspases, and cleaving PARP in MCF-7 breast cancer cells.

Compound 1, known as Apoptosis inducer 56, is administered orally to BALB/c mice at doses ranging from 1 to 10 mg/kg daily for 28 consecutive days. It remains safe at doses up to 10 mg/kg, showing no significant toxic effects on hematological, biochemical, renal, or liver-related parameters.