PKM2-IN-6 (compound 7d) is a potent PKM2 inhibitor that can be administered orally and demonstrates an IC 50 value of 23 nM. It triggers apoptosis and causes cell cycle arrest in the G2 phase, while also reducing the mRNA levels of both PKM1 and PKM2. Additionally, PKM2-IN-6 exhibits anticancer properties and shows promise for research in triple-negative breast cancer [1].

PKM2-IN-6 (compound 7d) exhibited cytotoxic activity in COLO-205, A-549, and MCF-7 cells with IC50 values of 18.33, 47.00, and 19.80 μM, respectively, after being incubated for 48 hours with concentrations ranging from 0 to 100 μM (0, 20, 40, 60, 80, 100 μM; 48 hours)[1]. The compound also induced apoptosis and caused cell cycle arrest at the G2 phase when tested at 14.38 μM over a 48-hour period[1]. Furthermore, PKM2-IN-6 significantly reduced the mRNA levels of PKM1 and PKM2 when administered at 14.38 μM for 24 hours[1]. In cytotoxicity assays, these results were consistent across the tested cell lines COLO-205, A-549, and MCF-7 under the specified conditions. RT-PCR analysis in 4T1 cells showed a marked reduction in PKM1 and PKM2 mRNA levels at a concentration of 14.38 μM after 24 hours of incubation. Apoptosis analysis demonstrated a significant reduction in viable cells and an increase in late-stage apoptotic and necrotic cells in both 2D and 3D cell cultures[1].

PKM2-IN-6, administered at doses of 25 and 50 mg/kg orally each day for three weeks, can reduce tumor volume and weight in female CD-1 nude mice (6-8 weeks) injected with 4T1-Red-FLuc cells [1].