Breast cancer (BC) is one of the main causes of cancer-associated death in women. And, BC is high recurrence and/or metastatic potential. BC is typically categorized into respective subtypes based on the presence of representative receptors (the human epidermal growth factor receptor, estrogen receptor, and progesterone receptor). Hence, these surface receptors are promising therapeutic targets for drug development against BCs. However, about 20% of BC does not express all of these three receptors and is classified as triple-negative breast cancer (TNBC). Due to a lack of particular therapeutic targets and an increased metastatic potential, TNBC patients usually show a relatively worse clinical outcome than patients with other BC subtypes. Metastatic triple-negative breast cancer (mTNBC) is a fatal type of BC, and signal transducer and activator of transcription 3 (STAT3) has emerged as an effective target for mTNBC. Hence, we will introduce a STAT3 inhibitor-MC0704.

MC0704 is a STAT3 inhibitor with an IC₅₀ value of 2.13 μM.

MC0704 is a β-carboline compound containing a p-bromo-benzyl ketone at the C-1 position and an N-ethyl 3-indole amide at the C-3 position. Importantly, MC0704 exhibited potential antitumor activity in acquired docetaxel-resistant TNBC cells in vitro and in vivo. In vitro, MC0704 (0-50 μM; 72 h) shows cytotoxicity to HEK-293, lung epithelial normal (MRC-5), MDA-MB 231, MDA-MB-231 paclitaxel-resistant (MDA-MB-231-PTR) and MDA-MB-231 docetaxel-resistant (MDA-MB-231-DTR) cells with IC₅₀ values of 3.11, 33.25, 2.98, 3.24 and 2.87 μM, respectively. In addition, MC0704 (0, 2.5, 5, and 10 μM; 36-48 h) increases the cell cycle arrest at the G2/M phase and induces apoptosis in MDA-MB-231-DTR cells. In vivo, MC0704 (10 mg/kg; i.p.; 10 mg/kg; once daily for 12 days) inhibits cancer growth of mice with MDA-MB-231-DTR cell transplant. Moreover, MC0704 in combination with docetaxel exhibited potent antitumor activities in a xenograft mouse model. All in all, the novel synthetic STAT3 pathway inhibitor, MC0704 is a hopeful agent for anti-TNBC.