PKM2-IN-3 is a potent PKM2 kinase inhibitor, displaying an IC 50 value of 4.1 μM. The compound effectively suppresses PKM2-mediated glycolysis and NLRP3 activation, thereby exerting an anti-neuroinflammatory effect.

PKM2:4.1 μM (IC50)

PKM2-IN-3 (compound 10i) effectively suppresses TNF-α secretion in LPS-induced RAW264.7 macrophages with an IC50 of 5.2 μM and demonstrates minimal toxicity with a CC50 of 43.6 μM[1]. At concentrations of 0.1-100 μM over 20 minutes, it selectively inhibits PKM2 kinase activity with an IC50 of 4.1 μM[1].

PKM2-IN-3, at a dosage of 1 and 10 mg/kg administered intraperitoneally (i.p.) daily for three days, significantly reversed behavior changes in LPS-induced mice during open field tests. Similarly, when administered intravenously (i.v.) at 4 hours and 24 hours post-ischemia, it notably reduced infarct volume and ameliorated neurological deficits in tMCAO rat models. In the first scenario, the treatment involved male mice aged 6-8 weeks and weighing 20.0-22.0 g, while in the second, male Sprague-Dawley rats aged 8-10 weeks and weighing 250.0-280.0 g were used.