LIQ1, a flavonoid derivative, is a potent Pyruvate kinase M2 ( PKM2 ) allosteric inhibitor ( IC50 = 0.39 μM; K d = 4.5 μM) targeting Arg43 within the polyarginine pocket. LIQ1 exhibits efficacy in a mouse model of LPS -induced endotoxemia, preventing the nuclear translocation of PKM2 and inhibiting its binding to HIF-1α, thereby suppressing IL-1β transcription. LIQ1 can be used for the research of endotoxemia [1].
In Vivo, LIQ1 (1, 2, and 5 mg/kg; i.p.; administered at 0, 12, 24, and 36 h after LPS injection) significantly improves survival and reduces inflammation and organ injury in LPS-induced endotoxemia in mice[1]. LIQ1 (20 mg/kg; i.p.; single dose or daily for 14 days) shows negligible acute toxicity and no hepatorenal toxicity in mice, supporting its favorable safety profile[1].
In Vitro, LIQ1 (100 μM; 2 h) significantly enhances the thermal stability of PKM2 within the tem-perature range of 40-52 °C, increasing its melting temperature (Tm) by 3.4 °C[1]. LIQ1 significantly reduces the inhibitory effect on PKM2 R43A (IC50 = 4.10 μM; Kd = 11.1 μM) compared to wild-type PKM2 (IC50 = 0.98 μM; Kd = 3.2 μM), indicating that R43 is a critical residue mediating the allosteric inhibition of PKM2[1].
References:
[1]. Wang X, et al. Discovery of liquiritigenin derivatives as PKM2 allosteric inhibitors via targeting the polyarginine pocket. Bioorg Chem. 2025;167:109212.
In Vivo, LIQ1 (1, 2, and 5 mg/kg; i.p.; administered at 0, 12, 24, and 36 h after LPS injection) significantly improves survival and reduces inflammation and organ injury in LPS-induced endotoxemia in mice[1]. LIQ1 (20 mg/kg; i.p.; single dose or daily for 14 days) shows negligible acute toxicity and no hepatorenal toxicity in mice, supporting its favorable safety profile[1].
In Vitro, LIQ1 (100 μM; 2 h) significantly enhances the thermal stability of PKM2 within the tem-perature range of 40-52 °C, increasing its melting temperature (Tm) by 3.4 °C[1]. LIQ1 significantly reduces the inhibitory effect on PKM2 R43A (IC50 = 4.10 μM; Kd = 11.1 μM) compared to wild-type PKM2 (IC50 = 0.98 μM; Kd = 3.2 μM), indicating that R43 is a critical residue mediating the allosteric inhibition of PKM2[1].
References:
[1]. Wang X, et al. Discovery of liquiritigenin derivatives as PKM2 allosteric inhibitors via targeting the polyarginine pocket. Bioorg Chem. 2025;167:109212.