Iminostilbene

Lu S, et al. Journal of Advanced Research, 2021, 29, 83-94.

Iminostilbene (ISB) has emerged as a promising therapeutic agent for myocardial ischemia/reperfusion (MI/R) injury by modulating macrophage-driven inflammation. This study highlights its cardioprotective potential and identifies its molecular mechanism of action.
Through in vivo and in vitro investigations, ISB demonstrated significant anti-myocardial injury effects, enhancing cardiac function, reducing infarction size, and suppressing macrophage-mediated inflammation. Proteomic analyses employing advanced techniques, including click chemistry-based activity profiling and competitive inhibition assays, pinpointed pyruvate kinase isozyme type M2 (PKM2) as the primary molecular target of ISB.
Binding studies, such as surface plasmon resonance (SPR), cellular thermal shift assay (CETSA), and drug-affinity responsive target stability (DARTS), revealed ISB's dose-dependent interaction with PKM2. This interaction downregulated PKM2 expression, subsequently reducing hypoxia-inducible factor 1-alpha (HIF1α) and phosphorylated STAT3, two key mediators of inflammatory pathways. This pioneering research underscores the therapeutic value of ISB in MI/R injury, demonstrating its dual role as an anti-inflammatory agent and a PKM2 modulator.