TNI-97 is a selective, orally active HDAC6 inhibitor with an IC50 value of 0.2 nM. It significantly suppresses the growth and colony-forming abilities of the triple-negative breast cancer (TNBC) cell line MDA-MB-453. In these cells, TNI-97 induces widespread cell death, including apoptosis, necroptosis, and pyroptosis. Additionally, TNI-97 demonstrates antitumor activity in mouse models bearing MDA-MB-453 xenograft tumors or syngeneic mouse-derived TNBC cell allograft tumors. TNI-97 is useful for researching triple-negative breast cancer.

HDAC6:0.2 nM

TNI-97 demonstrates antitumor activity in MDA-MB-453 cells and MDA-MB-468 cells, with GI 50 values of 0.2 μM and 5.4 μM, respectively. At a lower concentration of 1 μM for 24 hours, TNI-97 significantly induces α-tubulin acetylation in MDA-MB-453 cells more effectively than Ricolinostat (ACY-1215), while not inducing histone H3 acetylation. Additionally, TNI-97 inhibits colony formation in MDA-MB-453 cells in a dose-dependent manner at concentrations of 1-2 μM over 14 days. At 2.5-5 μM for 48 hours, TNI-97 induces apoptosis, necroptosis, and pyroptosis in MDA-MB-453 cells.

TNI-97, administered orally at doses of 20-40 mg/kg for 5 days on and 2 days off over a period of 5 weeks, demonstrates a dose-dependent inhibition of tumor growth in NSIG mice with MDA-MB-453 xenograft tumors. Additionally, TNI-97 at 40 mg/kg, given for 2 weeks under the same dosing schedule, significantly reduces both tumor weight and volume when used in combination with Paclitaxel in BALB/c mice bearing TNBC cell allograft tumors.