Select novel small-molecule uPA potential inhibitors as anti-cancer agents against breast cancer.

Cancer metastasis is a significant contributor to global morbidity and mortality rates. The urokinase type plasminogen activator (uPA) and its receptor (uPAR) play an essential role in facilitating abnormal cell metastasis and tumor progression. This research examines novel uPA/uPAR compounds as potential anticancer targets in various types of tumors. Several compounds were screened for their bioactivity and inhibitory effects on uPA and its receptor interactions, demonstrating the significant potential of a compound previously recognized as a promising uPA inhibitor, initially developed for the treatment of multiple sclerosis. The compounds exhibited notably low IC₅₀ values, as low as 1.4 μM, against the aggressive triple negative breast cancer cell line MDA-MB-231 compared to the chemotherapeutic drug Mitoxantrone. MDA-MB-231 cells treated with KCO241 and KCO246 exhibited selective anticancer activity, inducing apoptotic pathways and demonstrating selective anticancer efficacy. This study showed that these novel uPA inhibitors have potential therapeutic applications for the treatment of metastatic cancers and the modulation of disease progression. Subsequent preclinical in vivo investigations will further evaluate the safety as well as pharmacological characteristics and potential for translation.