PKM2-IN-12 is an orally active PKM2 inhibitor with an IC50 of 10 nM. It effectively hinders the proliferation and migration of COLO-205 cells, induces cell cycle arrest, and triggers apoptosis (apoptosis). PKM2-IN-12 significantly reduces lactate, pyruvate, and ROS levels in cells. In mouse models, it not only directly targets cancer cells but also restores disrupted intestinal microecological balance. PKM2-IN-12 is useful for colorectal cancer research.

PKM2:10 nM

PKM2-IN-12 (Compound 10j) exhibits varying levels of sensitivity across COLO-205, CAL-27, and MCF-7 cells with IC50 values of 4.21, 13.3, and 22.34 μM, respectively. At a concentration of 4.21 μM for 48 hours, PKM2-IN-12 primarily induces late apoptosis in COLO-205 cells and causes cell cycle arrest at the G2 phase. Moreover, PKM2-IN-12 significantly inhibits the migration capability of COLO-205 cells and reduces the levels of lactate, pyruvate, and reactive oxygen species (ROS) within these cells over a 0-48 hour period. It also increases the expression of PKM2 monomers and tetramers in COLO-205 cells, without affecting PKM1 expression.

PKM2-IN-12 (Compound 10j) administered at a dosage of 50-100 mg/kg orally every three days for 72 days effectively inhibits tumor growth in a colon cancer model associated with colitis (CAC) and reverses dysbiosis in the gut microbiota of mice.