2-D08

2-D08 is a synthetic small molecule identified as 2',3',4'-trihydroxyflavone and is best characterized as a **selective inhibitor of protein sumoylation**, targeting the SUMO (Small Ubiquitin-like Modifier) conjugation pathway[4][5][6][8]. It is cell-permeable and mechanistically unique among sumoylation inhibitors[5][6]. 2-D08 also exhibits inhibitory activity against several kinases, including Axl, IRAK4, ROS1, MLK4, GSK3β, RET, KDR, and PI3Kα, with low nanomolar IC50 values[2][6]. Functionally, 2-D08 has demonstrated notable **anticancer effects** through the induction of reactive oxygen species (ROS), apoptotic signaling (e.g., caspase-3 activation), cell-cycle arrest (increased p21 and p27 expression), and necrosis, especially in human uterine leiomyosarcoma (Ut-LMS) cells[1]. In preclinical studies, it suppresses proliferation, enhances apoptosis and necrosis, downregulates cell viability, and inhibits colony formation in tumor cells[1]. Recent research also identifies a **novel action on the Kir4.1 potassium channel** in oligodendrocyte precursor cells (OPCs), leading to **promoted remyelination** in animal models of multiple sclerosis and motor function improvement without inducing seizures—a side effect observed with existing MS therapies such as dalfampridine[3][7]. This suggests a therapeutic potential both as a SUMO pathway modulator and a neural repair agent in demyelinating diseases[3][7].

Other names

2',3',4'-trihydroxyflavone