ULK1-IN-3 (Compound 8) is a novel chalcone-based potential ULK1 inhibitor. This compound inhibits the cell cycle, autophagy, and induces apoptosis and oxidative stress in colorectal cancer cell lines.

ULK1-IN-3 demonstrates effective growth inhibition across various cell lines, including 786-O, MCF-7, SW620, and T-24 colon cancer cells when administered at concentrations ranging from 0-20 µM over 72 hours. This compound is particularly potent against the SW620 cells, with an LC50 value of 3.2 µM, slightly surpassing the efficacy of 5-Fluorouracil. In addition, ULK1-IN-3 at concentrations of 1.25-10 µM induces G2/M and S phase cell cycle arrest in SW620 cells after 24 hours. At concentrations of 1.25-5 µM over 48 hours, ULK1-IN-3 likely triggers the classical apoptotic pathway in SW620 cells by increasing the production of reactive oxygen species (ROS). Furthermore, ULK1-IN-3 upregulates the expression of cleaved PARP (cPARP), NFκβ, and AMPK, while downregulating AKT expression in SW620 cells.