TW-92

TW-92 is a synthetic chloro-amino-phenyl naphthoquinone derivative that has demonstrated potent anti-leukaemic activity, particularly against acute myeloid leukaemia (AML). It induces cell death through both apoptotic and necrotic pathways by triggering multiple intracellular signaling cascades. The compound's mechanism of action involves the rapid phosphorylation and activation of p38 mitogen-activated protein kinase (p38MAPK) and extracellular signal-regulated protein kinases (ERK1/2). Additionally, TW-92 promotes the generation of intracellular reactive oxygen species (ROS), such as hydrogen peroxide, via the activation of NADPH oxidase, leading to glutathione depletion. It also exerts a direct effect on mitochondria, causing swelling, loss of membrane potential, and the release of cytochrome c, which subsequently activates caspases. Furthermore, TW-92 modulates the expression of Bcl-2 family proteins by down-regulating the anti-apoptotic protein Mcl-1 and up-regulating the pro-apoptotic protein BAX.