Telomerase-IN-1 is a telomerase inhibitor (IC50: 0.19 μM). telomerase-IN-1 activates hTERT expression through the endoplasmic reticulum stress (ERS) of the ER overreaction (EOR), which then induces ERS, leading to apoptosis. telomerase-IN-1 leads to inhibition of cell proliferation through the expression of downstream signaling molecules including Telomease-IN-1 has high inhibitory activity against telomerase, high anti-proliferative capacity against SMMC-7721 cells, and no significant toxic effect on human normal hepatocytes. telomerase-IN-1 in xenograft tumor model exhibited antitumor activity.

Treatment of SMMC-7721 cells with Telomerase-IN-1 (20, 40, and 80 nM) for 48 hours results in significant accumulation of green fluorescence, demonstrating a decrease in mitochondrial membrane potential (MMP). At 40 nM, Telomerase-IN-1 notably enhances the expression of cytochrome c (cyt-c) and Bax, while reducing Bcl-2 levels. Our in vitro findings illustrate that Telomerase-IN-1 exhibits robust inhibitory effects on telomerase, displaying significant antiproliferative activity against SMMC-7721 cells without apparent toxicity towards human normal hepatocyte cells. Telomerase-IN-1 treatment reduces cancer cell growth in both dose- and time-dependent manners, with minimal impact on the viability of L-02 cells at 10 μM. A noteworthy increase in apoptosis is observed following 48 hours of treatment with Telomerase-IN-1 at concentrations of 20, 40, and 80 nM.

Our in vivo studies demonstrate a significant inhibition of tumor growth in xenograft tumor models by Telomerase-IN-1. Our findings indicate that the compound triggers endoplasmic reticulum stress (ERS) via an excessive ER response (EOR), leading to the activation of hTERT expression. Subsequently, this ERS induction, intricately linked to oxidative stress and mitochondrial dysfunction, initiates apoptotic cell death and modulates downstream signaling molecules, including CHOP (CAAT/enhancer-binding protein homologous protein), as well as the mitochondrion pathway of apoptosis. As a result, cell proliferation is effectively suppressed.[1]