HsClpP activator-2 is an orally active HsClpP agonist with a KD of 40 nM. It exhibits significant inhibitory effects on small cell lung cancer (SCLC) cells, including H69 (IC50 = 0.17 μM) and H82 (IC50 = 0.19 μM). This compound disrupts mitochondrial membrane potential (MMP), induces apoptosis (apoptosis), and promotes ROS production in H82 cells. Additionally, HsClpP activator-2 significantly suppresses tumor growth in non-SMC cell xenograft models and is applicable for research in small cell lung cancer (SCLC).

ClpP (human):40 nM (Kd)

HsClpP activator-2 (Compound 8o) demonstrates significant antiproliferative activity against H69, H82, and non-SMC cells with IC50 values of 0.17 μM, 0.19 μM, and 0.1 μM, respectively, when applied at concentrations of 0.02-10 μM for 72 hours. Additionally, HsClpP activator-2 at 100-400 nM over 72 hours induces degradation of mitochondrial OXPHOS complex proteins (NDUFB8, SDHB, UQCRC2, MTCO1, ATP5A) in a dose-dependent manner in H82 cells. It also significantly decreases intracellular ATP levels and increases ROS levels in H82 cells under the same conditions. Furthermore, HsClpP activator-2 disrupts mitochondrial membrane potential (MMP) and induces apoptosis in H82 cells at concentrations of 100-400 nM for 48-72 hours. Lastly, when applied to non-SMC cells at 100-400 nM for 24-48 hours, it inhibits colony formation and migration.

HsClpP activator-2 (Compound 8o) administered intraperitoneally at doses of 1.3-5 mg/kg twice weekly for 20 consecutive days demonstrates significant antitumor efficacy in male BALB/c nude mice bearing non-SMC cell xenograft tumors.